Nucleic acid vector, nucleic acid drug, preparation method therefor, and use thereof

Abstract

A nucleic acid vector, a nucleic acid drug, a preparation method therefor, and the use thereof. The nucleic acid vector comprises sequences a, b, and c; and the nucleic acid vector is selected from DNA, RNA or a DNA-RNA hybrid vector; sequences a, b, and c self-assemble to form the nucleic acid vector, and sequences a, b, and c comprise backbone sequences with the following core sequences: sequence a1 as represented by SEQ ID NOs 1 or 4, sequence b1 as represented by SEQ ID NOs 2 or 5 and sequence c1 as represented by SEQ ID NOs 3 or 6, or any variant sequence of at least one among sequence a1, sequence b1, and sequence c1, a variant sequence comprising the insertion, deletion, or substitution of at least one nucleobase; and the DNA-RNA hybrid vector is a vector formed by self-assembly of a combination of a DNA vector sequence and an RNA vector sequence. The vector has high delivery efficiency, and the delivery system is more stable. In addition, the preparation process is simpler and more efficient.

Description

Nucleic acid vector, nucleic acid drug, preparation method and application thereof

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to Chinese Patent Application No. 202310871667.8 filed on July 14, 2023, and the contents of the above-mentioned Chinese patent application disclosure are hereby incorporated by reference in their entirety as a part of this application. Technical Field

[0003] The present invention relates to the field of nucleic acid drugs, and in particular to a nucleic acid vector, a nucleic acid drug, and a preparation method and application thereof. Background Art

[0004] Single-stranded or double-stranded RNA drugs with a small molecular weight (the number of nucleotides usually does not exceed 100) are called "oligonucleotide drugs". Oligonucleotide drugs are a new drug category that is completely different from small molecule drugs and antibody drugs. Their drug composition is a nucleotide sequence, and their drug mechanism is to act on mRNA and inhibit the expression of target proteins through gene silencing (that is, oligonucleotide drugs act after gene transcription and before protein translation), thereby achieving the purpose of treating diseases. It is a strategic frontier area of ​​biopharmaceutical innovation.

[0005] Compared to antibody drugs, oligonucleotide drugs do not require complex protein modification and CMC development (process and quality control) during the R&D phase. The production process is relatively simple, not requiring large-scale mammalian cell fermentation and protein purification. They offer advantages such as a rich pool of candidate targets, a short R&D cycle, sustained efficacy, and a high success rate in clinical development. Oligonucleotide drugs deliver therapeutics at the post-transcriptional level, enabling breakthroughs in targeting specific, difficult-to-drugged protein targets. They are expected to address currently untreatable diseases, including genetic disorders and other intractable diseases. They hold tremendous potential for developing therapeutics for "undruggable" and "undruggable" diseases, and are expected to form the third wave of modern new drugs following small molecule and antibody drugs.

[0006] However, the following shortcomings of oligonucleotide drugs are key factors hindering their development: First, they are extremely fragile and easily degraded by nucleases in the body, making chemical modification difficult; second, they are generally immunotoxic and can easily cause serious side effects in the human body. Therefore, the delivery of oligonucleotide drugs and their combined applications remain a major bottleneck in this field that needs to be overcome.

[0007] In addition to the two clinically proven delivery technologies of LNP (lipid nanoparticles) and GalNAc, there are also reports of other delivery methods, such as the PNP (peptide nanoparticle) delivery technology developed by Shengnuo Pharmaceuticals, as well as GalAhead and GalNAc-PDoV technologies. PNP and LNP are both a type of organic nanoparticle delivery, but a single PNP is allowed to load multiple siRNAs, which can be used to develop multi-target nucleic acid drugs; the latter two have similar effects, which is equivalent to being able to deliver more than one siRNA on the basis of GalNAc. This type of delivery system is mainly aimed at siRNA drugs, and the delivery system for other types of oligonucleotide drugs still faces challenges. Therefore, the efficiency, drug type and reliability of nucleic acid drug delivery still need to be further improved.

[0008] Summary of the Invention

[0009] The main purpose of the present invention is to provide a nucleic acid vector, a nucleic acid drug and its preparation method and application, so as to solve the problem of low delivery efficiency of various oligonucleotide drugs in the prior art, especially the difficulty in delivering multiple oligonucleotide drugs simultaneously.

[0010] To achieve the above object, according to one aspect of the present invention, a nucleic acid vector is provided, comprising a sequence a, a sequence b, and a sequence c, the nucleic acid vector being selected from a DNA vector, an RNA vector, or a DNA-RNA hybrid vector; the sequence a, the sequence b, and the sequence c self-assemble to form the nucleic acid vector, wherein the sequence a, the sequence b, and the sequence c comprise a vector backbone sequence, the vector backbone sequence comprising the following core sequences: a1 sequence, b1 sequence, and c1 sequence, or any variant sequence of at least one of the a1 sequence, b1 sequence, and c1 sequence, the variant sequence comprising an insertion, deletion, or substitution of at least one base; in the DNA vector, the sequence a1 is SEQ ID NO: 1, the sequence b1 is SEQ ID NO: 2, and the sequence c1 is SEQ ID NO: 3; in the RNA vector, the sequence a1 is SEQ ID NO: 4, the sequence b1 is SEQ ID NO: 5, and the sequence c1 is SEQ ID NO: 6; wherein the DNA-RNA hybrid vector is a vector self-assembled by a combination of the sequences of the DNA vector and the RNA vector; SEQ ID NO: 1: ACGAGCGTTCCG; SEQ ID NO: 2: CGGTTCGCCG; SEQ ID NO: 3: SEQ ID NO: 4 NO: 3: CGGCCATAGCCGT; SEQ ID NO: 4: ACGAGCGUUCCG; SEQ ID NO: 5: CGGUUCGCCG; SEQ ID NO: 6: CGGCCAUAGCCGU.

[0011] Furthermore, the vector backbone sequence further includes a first extension segment and an optional second extension segment, and the first extension segment and the second extension segment are located at the 5' end and / or 3' end of any sequence among the a1 sequence, the b1 sequence and the c1 sequence; preferably, the first extension segment and the second extension segment are each independently 1 to 14 nt; preferably, the first extension segment is selected from any one or more of the following DNA extension segments or RNA extension segments corresponding to the DNA extension segment; 1) 5' end of the a1 sequence: GACGCCC, 3' end of the c1 sequence: GGGCGTC; 2) 3' end of the a1 sequence: GGAGAGG, 5' end of the b1 sequence: CCTCTCC; 3) 3' end of the b1 sequence: CGAGCC, 5' end of the c1 sequence: GGCTCG or GGCACG; 4) 5' end of the a1 sequence: GGCGCCC or GACGCCC, 3' end of the c1 sequence: GGGCGCC; 5) a 1 sequence 3' end: GGAG, b1 sequence 5' end: CTCC; 6) b1 sequence 3' end: CCAGCC, c1 sequence 5' end: GGCACG or GGCTCG; Preferably, the second extension segment is selected from any one or more of the following DNA extension segments or RNA extension segments corresponding to the DNA extension segment: 1) a1 sequence 5' end: C or GC, c1 sequence 3' end: GC or GCT; 2) a1 sequence 3' end: AG, AGC or AGCT, b1 sequence 5' end: GCT or CT; 3) b1 sequence 3' end: GC, GCG or GCGT, c1 sequence 5' end: GC or CGC; 4) a1 sequence 3' end: C, AGGCC, AGGCCT or AGGAG, b1 sequence 5' end: G, GGCCT or CTCCT; 5) b1 sequence 3' end: GCC or GCCT, c1 sequence 5' end: GGC.

[0012] Furthermore, the nucleic acid vector further comprises a single-stranded bonding bridge sequence and / or a transition sequence, wherein the single-stranded bonding bridge sequence is selected from any one or more of the following: 1) located at the 3' end of the backbone sequence of sequence a: SEQ ID NO: 7: TGTAGCACGGTGGC or its complementary sequence SEQ ID NO: 8: GCCACCGTGCTACA; 2) located at the 3' end of the backbone sequence of sequence b: SEQ ID NO: 9: TCGGCGCGGCCGTG or its complementary sequence SEQ ID NO: 10: CACGGCCGCGCCGA; 3) located at the 3' end of the backbone sequence of sequence c: SEQ ID NO: 11: TGCTGCTGCTGCTG or its complementary sequence SEQ ID NO:12: CAGCAGCAGCAGCA; wherein the transition sequence is a sequence formed by n consecutive U, T or A, where n is a natural number of 2 to 8, preferably 3 to 6, or a sequence of a random combination of A, U, T, C and / or G, and the transition sequence is located at the 5' end or 3' end of the core sequence; preferably, the a sequence, b sequence and c sequence in the nucleic acid vector are as follows:

[0013] a sequence is: SEQ ID NO: 15: GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC, wherein the underlined portion is a single-stranded connecting bridge sequence;

[0014] b sequence is: SEQ ID NO: 16: CCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, wherein the underlined portion is a single-stranded connecting bridge sequence;

[0015] c sequence is: SEQ ID NO: 17: GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG, wherein the underlined portion is a single-stranded connecting bridge sequence; or

[0016] The a sequence, b sequence and c sequence in the nucleic acid vector are as follows:

[0017] a sequence is: SEQ ID NO: 18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC;

[0018] b sequence is: SEQ ID NO: 19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG;

[0019] The c sequence is:

[0020] SEQ ID NO: 20: CAGCAGCAGCAGCACGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the underlined portion is the single-stranded connecting bridge sequence.

[0021] Furthermore, the backbone sequence for self-assembly to form the nucleic acid vector is selected from any of the following groups:

[0022] 1) a sequence: SEQ ID NO: 21: GCGACGCCCACGAGCGTTCCGGGAGAGGAG,

[0023] b Sequence: SEQ ID NO:22: CTCCTTCCCGGTTCGCCGCGAGCCGCG,

[0024] c sequence: SEQ ID NO: 23: CGCGGCACGCGGCCATAGCCGTGGGCGTCGC;

[0025] 2) a sequence: SEQ ID NO: 24: GCGACGCCCACGAGCGTTCCGGGAGAGGAGCT,

[0026] b sequence: SEQ ID NO: 19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG,

[0027] c sequence: SEQ ID NO: 23: CGCGGCACGCGGCCATAGCCGTGGGCGTCGC;

[0028] 3) a sequence: SEQ ID NO: 24: GCGACGCCCACGAGCGTTCCGGGAGAGGAGCT,

[0029] b sequence: SEQ ID NO:25: GCTCCTCTCCCGGTTCGCCGCGAGCCGCGT,

[0030] c sequence: SEQ ID NO: 26: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGCT;

[0031] 4) a sequence: SEQ ID NO: 24: GCGACGCCCACGAGCGTTCCGGGAGAGGAGCT,

[0032] b sequence: SEQ ID NO:25: GCTCCTCTCCCGGTTCGCCGCGAGCCGCGT,

[0033] c sequence: SEQ ID NO:27: CGCGGCACGCGGCCATAGCCGTGGGCGTCGCT;

[0034] 5) a sequence: SEQ ID NO:28: GACGCCCACGAGCGTTCCGGGAGAGG,

[0035] b sequence: SEQ ID NO:29: CCTCTCCCGGTTCGCCGCGAGCC,

[0036] c sequence: SEQ ID NO:30: GGCTCGCGGCCATAGCCGTGGGCGTC;

[0037] 6) a sequence: SEQ ID NO:18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC,

[0038] b sequence: SEQ ID NO:19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG,

[0039] c sequence: SEQ ID NO:31: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGC;

[0040] 7) a sequence: SEQ ID NO:24: GCGACGCCCACGAGCGTTCCGGGAGAGGAGCT,

[0041] b sequence: SEQ ID NO:19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG,

[0042] c sequence: SEQ ID NO:26: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGCT;

[0043] 8) a sequence: SEQ ID NO:24: GCGACGCCCACGAGCGTTCCGGGAGAGGAGCT,

[0044] b sequence: SEQ ID NO:19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG,

[0045] c sequence: SEQ ID NO:31: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGC;

[0046] 9) Sequence a: SEQ ID NO:24: GCGACGCCCACGAGCGTTCCGGGAGAGGAGCT,

[0047] Sequence b: SEQ ID NO:25: GCTCCTCTCCCGGTTCGCCGCGAGCCGCGT,

[0048] Sequence c: SEQ ID NO:26: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGCT;

[0049] 10) Sequence a: SEQ ID NO:24: GCGACGCCCACGAGCGTTCCGGGAGAGGAGCT,

[0050] Sequence b: SEQ ID NO:25: GCTCCTCTCCCGGTTCGCCGCGAGCCGCGT,

[0051] Sequence c: SEQ ID NO:31: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGC;

[0052] 11) Sequence a: SEQ ID NO:18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC;

[0053] Sequence b: SEQ ID NO:25: GCTCCTCTCCCGGTTCGCCGCGAGCCGCGT;

[0054] Sequence c: SEQ ID NO:26: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGCT;

[0055] 12) Sequence a: SEQ ID NO:32: CGACGCCCACGAGCGTTCCGGGAGAGGAGC;

[0056] Sequence b: SEQ ID NO:19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG;

[0057] Sequence c: SEQ ID NO:31: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGC;

[0058] 13) Sequence a: SEQ ID NO:33: GCGGCGCCCACGAGCGTTCCGGGAGC;

[0059] b sequence: SEQ ID NO:34: GCTCCCGGTTCGCCGCCAGCCGCC;

[0060] c sequence: SEQ ID NO:35: GGCGGCAGGCGGCCATAGCCGTGGGCGCCGC;

[0061] 14) a sequence: SEQ ID NO:36: GCGGCGCCCACGAGCGTTCCGGGAGAGGCC;

[0062] b sequence: SEQ ID NO:37: GGCCTCTCCCGGTTCGCCGCCAGCCGCC;

[0063] c sequence: SEQ ID NO:38: GGCGGCTGGCGGCCATAGCCGTGGGCGCCGC;

[0064] 15) a sequence: SEQ ID NO:39: GCGGCGCCCACGAGCGTTCCGGGAGAGGCCT;

[0065] b sequence: SEQ ID NO:40: GGCCTCTCCCGGTTCGCCGCCAGCCGCCT;

[0066] c sequence: SEQ ID NO:41: GGCGGCTGGCGGCCATAGCCGTGGGCGCCGCT;

[0067] 16) a sequence: SEQ ID NO:42: GCGGCGCCCACGAGCGUUCCGGGAGAGGCC;

[0068] b sequence: SEQ ID NO:43: GGCCUCUCCCGGUUCGCCGCCAGCCGCC;

[0069] c sequence: SEQ ID NO:44: GGCGGCUGGCGGCCAUAGCCGUGGGCGCCGC;

[0070] 17) a sequence: SEQ ID NO:45: CGACGCCCACGAGCGTTCCGGGAGAGGAG;

[0071] b sequence: SEQ ID NO:46: CTCCTCTCCCGGTTCGCCGCCAGCCGCC;

[0072] c sequence: SEQ ID NO:35: GGCGGCAGGCGGCCATAGCCGTGGGCGCCGC;

[0073] 18) a sequence: SEQ ID NO:36: GCGGCGCCCACGAGCGTTCCGGGAGAGGCC;

[0074] b sequence: SEQ ID NO:43: GGCCUCUCCCGGUUCGCCGCCAGCCGCC;

[0075] c sequence: SEQ ID NO:44: GGCGGCUGGCGGCCAUAGCCGUGGGCGCCGC;

[0076] 19) a sequence: SEQ ID NO:36: GCGGCGCCCACGAGCGTTCCGGGAGAGGCC;

[0077] b sequence: SEQ ID NO:40: GGCCTCTCCCGGTTCGCCGCCAGCCGCCT;

[0078] c sequence: SEQ ID NO:38: GGCGGCTGGCGGCCATAGCCGTGGGCGCCGC;

[0079] 20) a sequence: SEQ ID NO:36: GCGGCGCCCACGAGCGTTCCGGGAGAGGCC; <00,00198>b sequence: SEQ ID NO:40: GGCCTCTCCCGGTTCGCCGCCAGCCGCCT;

[0081] c sequence: SEQ ID NO:41: GGCGGCTGGCGGCCATAGCCGTGGGCGCCGCT;

[0082] 21) a sequence: SEQ ID NO:36: GCGGCGCCCACGAGCGTTCCGGGAGAGGCC;

[0083] b sequence: SEQ ID NO:37: GGCCTCTCCCGGTTCGCCGCCAGCCGCC;

[0084] c sequence: SEQ ID NO:44: GGCGGCUGGCGGCCAUAGCCGUGGGCGCCGC;

[0085] 22) Sequence a: SEQ ID NO:33: GCGGCGCCCACGAGCGTTCCGGGAGC;

[0086] Sequence b: SEQ ID NO:46: CTCCTCTCCCGGTTCGCCGCCAGCCGCC;

[0087] Sequence c: SEQ ID NO:35: GGCGGCAGGCGGCCATAGCCGTGGGCGCCGC;

[0088] 23) Sequence a: SEQ ID NO:47: GCGGCGCCCACGAGCGTTCCGGGAGAGGAG;

[0089] Sequence b: SEQ ID NO:46: CTCCTCTCCCGGTTCGCCGCCAGCCGCC;

[0090] Sequence c: SEQ ID NO:35: GGCGGCAGGCGGCCATAGCCGTGGGCGCCGC;

[0091] 24) Sequence a: SEQ ID NO:48: CGCCCACGAGCGTTCCGGGAGA;

[0092] Sequence b: SEQ ID NO:49: TCTCCCGGTTCGCCGCGAG;

[0093] Sequence c: SEQ ID NO:50: CTCGCGGCCATAGCCGTGGGCG;

[0094] 25) Sequence a: SEQ ID NO:51: UCGCCCACGAGCGUUCCGGGAGA;

[0095] Sequence b: SEQ ID NO:52: UCUCCCGGUUCGCCGCGAG;

[0096] Sequence c: SEQ ID NO:53: UCUCGCGGCCAUAGCCGUGGGCG;

[0097] 26) Sequence a: SEQ ID NO:54: GCGCCCACGAGCGTTCCGGGAGAGC;

[0098] Sequence b: SEQ ID NO:55: CCCUGCTCTCCCGGTTCGCCGCCAGCCGCC;

[0099] c sequence: SEQ ID NO: 56: GGCGGCAGGCGGCCATAGCCGTGGGCGC.

[0100] Furthermore, at least one of the base, ribose and phosphate in sequence a, sequence b and sequence c has at least one modifiable site, and any modifiable site has at least one of the following modifications: -F, methyl, amino, disulfide, carbonyl, carboxyl, sulfhydryl, aldehyde and thio; preferably, some of the phosphate backbones in sequence a, sequence b and sequence c have thio modifications; preferably, when the nucleic acid vector is an RNA vector or a DNA-RNA mixed vector, C and U in the RNA form of the nucleic acid vector have 2'-F modification, and A and G have 2'-OMe modification.

[0101] In the second aspect of the present application, a nucleic acid drug is provided, which includes any of the aforementioned nucleic acid vectors and a bioactive substance mounted on the nucleic acid vector, the bioactive substance including an oligonucleotide effector molecule and a targeting molecule for targeted delivery of the oligonucleotide molecule, wherein the oligonucleotide effector molecule is selected from at least one of the following: a nucleic acid immunostimulant, a nucleic acid aptamer, siRNA, miRNA and ASO; and when the oligonucleotide effector molecule includes a nucleic acid aptamer, the targeting molecule at least includes a nucleic acid aptamer; when the oligonucleotide effector molecule does not include a nucleic acid aptamer, the targeting molecule at least includes a small molecule compound with a targeting effect.

[0102] Furthermore, the nucleic acid immunostimulatory agent includes one or more of CpG2006, a variant of CpG2006, CpG1826, CpG2216, CpG2395, CpG-ODNT7 and CpG-BYZD.

[0103] Preferably, the sequence of CpG2006 is:

[0104] SEQ ID NO:57: TCGTCGTTTTGTCGTTTTGTCGTT or

[0105] SEQ ID NO: 58: UCGUCGUUUUGUCGUUUUGUCGUU;

[0106] Preferably, the sequence of the CpG2006 variant is: GTCGTT;

[0107] Preferably, the sequence of CpG1826 is: SEQ ID NO: 59: TCCATGACGTTCCTGACG;

[0108] Preferably, the sequence of CpG2216 is: SEQ ID NO: 60: GGGGGACGATCGTCGGGGGG;

[0109] Preferably, the sequence of CpG2395 is: SEQ ID NO: 61: TCGTCGTTTTCGGCGCGCGCCG;

[0110] Preferably, the sequence of CpG-ODNT7 is: SEQ ID NO: 62: TCGTCGTCGTCGTCGTCGTCG or SEQ ID NO: 63: TCGTCGTCGTCGTCGTCGTCGTCG;

[0111] Preferably, the sequence of CpG-BYZD is: AGCGAA.

[0112] Furthermore, the siRNA includes siRNA of any one or more of the following molecules: ASAP1, ATAD2, CD24, CD47, EGFR, HBV, HSP, HS70, PD-L1, PAPP-1, Survivin, TAP, TIM-3, TGF-β1 and VEGF-C.

[0113] Preferably, the siRNA of ASAP1 is selected from any one of the following: i) sense chain: SEQ ID NO: 64: AUUUGCUUCCAUAAUAUCAUU, antisense chain: SEQ ID NO: 65: UGAUAUUAUGGAAGCAAAUUU; ii) sense chain: SEQ ID NO: 66: UUAGGUUUGGGGUUGGAUCUU, antisense chain: SEQ ID NO: 67: GAUCCAACCCCAAACCUAAUU.

[0114] Preferably, the antisense strand of siRNA of ATAD2 is SEQ ID NO: 68: GCGUCGAAGUUGUAGGAUUUU, and the sense strand is SEQ ID NO: 69: AAUCCUACAACUUCGACGCUU.

[0115] Preferably, the sense strand of the CD24 siRNA is SEQ ID NO: 70: UGUUUACAUUGUUGAGGUAUU, and the antisense strand is SEQ ID NO: 71: UACCUCAACAAUGUAAACUUU.

[0116] Preferably, the siRNA for CD47 is selected from any one of the following: i) sense chain: SEQ ID NO: 72: GGUGAUUACCCAGAGAUAUTT, antisense chain: SEQ ID NO: 73: AUAUCUCUGGGUAAUCACCTT; ii) sense chain: SEQ ID NO: 74: UGGUGAAAGAGGUCAUUCCUU, antisense chain: SEQ ID NO: 75: GGAAUGACCUCUUUCACCAUU; iii) sense chain: SEQ ID NO: 76: GGAAUGACCUCUUUCACCATT, antisense chain: SEQ ID NO: 77: UGGUGAAAGAGGUCAUUCCTT; iv) sense chain: SEQ ID NO: 78: GGUGAUUACCCAGAGAUAUUU, antisense chain: SEQ ID NO: 79: AUAUCUCUGGGUAAUCACCUU.

[0117] Preferably, the siRNA for EGFR is selected from any one of the following: i) sense chain: SEQ ID NO: 80: GGCUGGUUAUGUCCUCAUUUU, antisense chain: SEQ ID NO: 81: AAUGAGGACAUAACCAGCCUU; ii) sense chain: SEQ ID NO: 82: CCUUAGCAGUCUUAUCUAAUU, antisense chain: SEQ ID NO: 83: UUAGAUAAGACUGCUAAGGUU; iii) sense chain: SEQ ID NO: 84: UGCCUUAGCAGUCUUAUCUAAUU, antisense chain: SEQ ID NO: 85: UUAGAUAAGACUGCUAAGGCAUU; iv) sense chain: SEQ ID NO: 86: UGCCUUAGCAGUCUUAUCUAAUUU, antisense chain: SEQ ID NO: 87: AAUUAGAUAAGACUGCUAAGGCAUU.

[0118] Preferably, the sense strand of the HBV siRNA is: SEQ ID NO: 88: GGACUUCUCUCAAUUUUCUUU, and the antisense strand is: SEQ ID NO: 89: AGAAAAUUGAGAGAAGUCCUU.

[0119] Preferably, the sense strand of the siRNA of HSP is: SEQ ID NO: 90: CGCAGAACCGUGUUCGAUU, and the antisense strand is: SEQ ID NO: 91: UCGAACACGGUGUUCUGCGUU.

[0120] Preferably, the sense strand of the siRNA of HS70 is: SEQ ID NO: 92: GGCCAACAAGAUCACCAUCUU, and the antisense strand is: SEQ ID NO: 93: GAUGGUGAUCUUGUUGGCCUU.

[0121] Preferably, the siRNA for PD-L1 is selected from any one of the following: i) sense chain: SEQ ID NO: 94: CCAGCACACUGAGAAUCAAUU, antisense chain: SEQ ID NO: 95: UUGAUUCUCAGUGUGCUGGUU; ii) sense chain: SEQ ID NO: 96: AGACGUAAGCAGUGUUGAATT, antisense chain: SEQ ID NO: 97: UUCAACACUGCUUACGUCUTT.

[0122] Preferably, the siRNA for PAPP-1 is: sense strand: SEQ ID NO: 98: GAGGAAGGUAUCAACAAAUTT, antisense strand: SEQ ID NO: 99: AUUUGUUGAUACCUUCCUCTT.

[0123] Preferably, the siRNA of Survivin is selected from any one of the following: i) sense chain: SEQ ID NO: 100: GCAGGUUCCUUAUCUGUCACAUU, antisense chain: SEQ ID NO: 101: UGUGACAGAUAAGGAACCUGCUU; ii) sense chain: SEQ ID NO: 102: GGAAUUGGAAGGCUGGGAACCUU, antisense chain: SEQ ID NO: 103: GGUUCCCAGCCUUCCAAUUCCUU; iii) sense chain: SEQ ID NO: 104: UGCAGGUUCCUUAUCUGUCATT, antisense chain: SEQ ID NO: 105: UGACAGAUAAGGAACCUGCTT; iv) sense chain: SEQ ID NO: 106: CUGCAGGUUCCUUAUCUGUCACAUU, antisense chain: SEQ ID NO: 107: UGUGACAGAUAAGGAACCUGCAGUU.

[0124] Preferably, the siRNA of TAP is selected from any one of the following: i) sense chain: SEQ ID NO: 108: GCUGCACACGGUUCAGAAUUU, antisense chain: SEQ ID NO: 109: AUUCUGAACCGUGUGCAGCUU; ii) sense chain: SEQ ID NO: 110: CAGGAUGAGUUACUUGAAAUU, antisense chain: SEQ ID NO: 111: UUUCAAGUAACUCAUCCUGUU.

[0125] Preferably, the sense strand of the TIM-3 siRNA is: SEQ ID NO: 112: GUGCUCAGGACUGAUGAAATT, and the antisense strand is: SEQ ID NO: 113: UUUCAUCAGUCCUGAGCACTT.

[0126] Preferably, the TGF-β1 siRNA is selected from any one of the following: i) sense chain: SEQ ID NO: 114: GUCAACUGUGGAGCAACACUU, antisense chain: SEQ ID NO: 115: GUGUUGCUCCACAGUUGACUU; ii) sense chain: SEQ ID NO: 116: GCAACAACGCCAUCUAUGATT, antisense chain: SEQ ID NO: 117: UCAUAGAUGGCGUUGUUGCTT.

[0127] Preferably, the siRNA of VEGF-C is selected from any one of the following: i) sense chain: SEQ ID NO: 118: GCAAGACGUUGUUUGAAAUUAUU, antisense chain: SEQ ID NO: 119: UAAUUUCAAACAACGUCUUGCUU; ii) sense chain: SEQ ID NO: 120: CAGCAAGACGUUGUUUGAAAUUAUU, antisense chain: SEQ ID NO: 121: UAAUUUCAAACAACGUCUUGCUGUU; iii) sense chain: SEQ ID NO: 122: CAGGAUGGUAAAGACUACAUU, antisense chain: SEQ ID NO: 123: UGUAGUCUUUACCAUCCUGUU.

[0128] Preferably, the ASO includes one or more of A-miR21, A-miR-10a, A-miR-30c and AmiR1306, and the miRNA includes one or more of miR-34, miR-542, miR-126 and miR-122.

[0129] Preferably, A-miR21 is selected from any one of the following DNA or RNA forms:

[0130] i)GATAAGCT;

[0131] ii) SEQ ID NO: 124: GTCAACATCAGTCTGATAAGCTA;

[0132] iii) SEQ ID NO: 125: TCAACATCAGTCTGATAAGCTA.

[0133] iv) T in i) or ii) is replaced by U;

[0134] Preferably, A-miR-10a is ACAGGGTA;

[0135] Preferably, A-miR-30c is SEQ ID NO: 126: GCTGAGAGTGTAGGATGTTTACA;

[0136] Preferably, the sequence of miR-34 is: TGTGACAAG;

[0137] Preferably, the sequence of miR-542 is: TGGCAGTGT;

[0138] Preferably, the sequence of miR-126 is: UCGUACC; or UCGUACCG; or CGTACCG or GTCGTT;

[0139] Preferably, the sequence of miR-122 is: GGAAGTGT;

[0140] Preferably, the sequence of AmiR1306 is: SEQ ID NO: 127: CATCACCACCAGAGCCAACGTC.

[0141] Furthermore, the nucleic acid aptamer includes a nucleic acid aptamer in the form of DNA or a nucleic acid aptamer in the form of RNA; preferably, the nucleic acid aptamer in the form of DNA includes at least one of the following aptamers: A1, A15, AS1411, AFP, ATP, Act-12c, A18, BAF7-1, C-MetSL-1, CH6, CA2, CRAC Orail target, CEA, CEA-18, CEA-T84, CSC1, CSC13, CD40, CD16a, CD19, CD3-4, CD44, CD12, CD20, CD24, CD24A-2, CD33, CD38, CD105, CD117, CD63, CD123, EGFR, EpCAM, EcR, FAP, GPC1, GPC3, GSK836, HBsAg, Her2, Her3, H MGA2, H2, IFN-γ, IL-4Ra, IL-17, LZH8, MUC1, M5, M7, M1, N5, NG-Dua, NKG2D_#-20-N-15, NSE, SARS-CoV-2- N15, SARS-CoV-2-N48, SARS-CoV-2-N58, SARS-CoV-2-N61, OX40, PSMA, PDGFRβ, PDGF, PD-L1, PD1, PTK-7, ProGRP-48, SF, TBA15, TBA29, TIMC-d, TRRA4, TFRA3, TTA1, TLS9a, TGF-βII, TNF-α, TNF, T1, Vap7, VEGF121, VEG F-V7t1, VCAM-1, VCAM-12d, AX02, AX104, PL-45, EP166, AGC, Karpas299, SW620, MDA-MB-231, MCF-7 and PC-3; RNA form The nucleic acid aptamer includes at least one of the following aptamers: A15, AS1411, BCMA, CTLA-4, CCL1, CEA, CD4-3, CD28, CD44, IL-4RA, EGFR, EpCAM, FGF2, FGF5, Her2, Her3, LAG-3, MUC1, MRP1, OX40, PSMA, PDGFRβ, TFRA4, TFRA3, TTA1, TIM3, TIMC-11, VEGF, VEGF165 and 4-1BB.

[0142] Preferably, the nucleic acid aptamer is selected from aptamers of at least one of the following sequences:

[0143] The A1 aptamer is:

[0144] SEQ ID NO: 128: GGTTGCATGCCGTGGGGAGGGGGGTGGGTTTTATAGCGTACTCAG;

[0145] The A15 aptamer is: SEQ ID NO: 129: CCCTCCTACATAGGG or SEQ ID NO: 130: CCCUCCUACAUAGGG;

[0146] The AS1411 aptamer is:

[0147] 1) SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG; or

[0148] 2) SEQ ID NO: 132: GGUGGUGGUGGUUGUGGUGGUGGUGG; or

[0149] 3) SEQ ID NO: 133: AUUCUGAACCGUGUGCAGCACCACGCUGCACACGGUUCAGAAUACACA;

[0150] The AFP aptamers are:

[0151] SEQ ID NO: 134: GGCAGGAAGACAAACAAGCTTGGCGGCGGGAAGGTGTTTAAATTCCCGGGTCTGCGTGGTCTGTGGTGCTGT;

[0152] The ATP aptamer is: SEQ ID NO: 135: ACCTGGGGAGTATTGGGGAGGAAGG, or SEQ ID NO: 136: GGGAGGACGATGCGGAGGAAGGGTAGG;

[0153] The Act-12c aptamer is:

[0154] SEQ ID NO: 137: CGGGGAAAGTCACGGGGGGTTTCAGATGTTCTGATCGGTGTGGAG;

[0155] The A18 aptamer is: SEQ ID NO: 138: CCAGATAGTCCCTGG;

[0156] The BAF aptamer is: SEQ ID NO: 139: GATAACGGGCACGAATTCGGAGTG;

[0157] The BCMA aptamers are:

[0158] SEQ ID NO: 140: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUAC;

[0159] The CTLA-4 aptamer is: 1) SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU; or 2) SEQ ID NO: 142: TCCCTACGGCGCTAACGATGGTGAAAATGGGCCTAGGGTGGACGGTGCCACCGTGCTACAAC;

[0160] The C-Met-SL1 aptamer is:

[0161] SEQ ID NO: 143: ATCAGGCTGGATGGTAGCTCGGTCGGGGTGGGTGGGTTGGCAAGTCTGAT;

[0162] The CH6 aptamer is:

[0163] SEQ ID NO: 144: AGTCTGTTGGACCGAATCCCGTGGACGCACCCTTTGGACG;

[0164] The CA2 aptamer is: SEQ ID NO: 145: CCCACGTCTGCGCTTAGCTCCTGGGCCTGGATGGGC;

[0165] The CCL1 aptamers are:

[0166] SEQ ID NO:146:UGACUCCUCUGACAGCCUAAUUUCUCCCGAUUACCCUG;

[0167] CRAC Orail target aptamers are:

[0168] SEQ ID NO: 147: CCAGTAGCCATACCGGTTTGTGGATGGGGTGTATGCGAGT;

[0169] The CEA aptamers are:

[0170] 1) SEQ ID NO: 148: CTAGGATCCCCACTCACCATCTCTCAGCTTGCTTCCTAGC; or

[0171] 2) SEQ ID NO: 149: CUAGGAUCCCCACUCACCAUCUCUCAGCUUGCUUCCUAGC; or

[0172] 3) SEQ ID NO:150: TTAACTTATTCGACCATA; or

[0173] 4) SEQ ID NO: 151: TCGCGCGAGTCGTCTGGGGAACCATCGAGTTACACCGACCTTCTATGTGCGGCCCCCCGCATCGTCCTCCC;

[0174] The CSC1 aptamers are:

[0175] SEQ ID NO: 152: ACCTTGGCTGTCGTGTTGTAGGTGGTTTGCTGCGGTGGGCTCAAGAAGAAAGCGCAAAGAGGTCAGTGGTCAGAGCGT;

[0176] The CSC13 aptamers are:

[0177] SEQ ID NO: 153: ACCTTGGCTGTCGTGTTGTGGGGTGTCGTATCTTTCGTGTCTTATTATTTTCTAGGTGGAGGTCAGTGGTCAGAGCGT;

[0178] The CD40 aptamers are:

[0179] 1) SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG;

[0180] 2) SEQ ID NO: 155: AGAGACGATGCGGCCAACGAGTAGGCGATAGCGCGTGGCAGAGCGTCGCT;

[0181] 3) SEQ ID NO: 156: GCCAACGAGTAGGCGATAGCGCGTGGC;

[0182] The CD16a aptamers are:

[0183] SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG;

[0184] The CD19 aptamers are:

[0185] 1) SEQ ID NO: 158: TGCGTGTGTAGTGTGTGTCGTTTCTCCTTTTTTTGGTTGCTGCTCTTAGGGATTTGGGCGG; or

[0186] 2) SEQ ID NO: 159: TGCGTGTGTAGTGTGTCTGTTCTCCTTTTTTTGGTTGCTGCTCTTAGGGATTTGGGCGG,

[0187] The CD4-3 aptamers are:

[0188] SEQ ID NO: 161: GGGAGGACGAUGCGGUUUGGGGUUUUCCCGUGCCCCAGACGACUCGCCCGA;

[0189] The CD3-4 aptamers are:

[0190] SEQ ID NO: 162: TCTCGGACGCGTGTGGTCGGCCGAGTGGCCCACGGTAGAAGGGTTAGAACTGCTGGTTGGTGAATCTCGCTGCCTGGCCCTAGAGTG;

[0191] The CD44 aptamers are:

[0192] SEQ ID NO: 163: CCAAGGCCTGCAAGGGAACCAAGGACACAG;

[0193] The CD12 aptamers are:

[0194] SEQ ID NO: 164: GTGGATTGTTGTGTTCTGTTGGTTTTTGTGTTGTC;

[0195] The CD20 aptamers are:

[0196] SEQ ID NO: 165: TGCGTGTGTAGTGTGTCTGTTTTTTATCTTCTTTTATCTACTCTTAGGGATTTGGGCGG;

[0197] The CD24 aptamers are:

[0198] SEQ ID NO: 166: TATGTGGGTGGGTGGGCGGTTATGCTGAGTCAGCCTTGCT;

[0199] The CD24A-2 aptamer is:

[0200] SEQ ID NO: 167: ATCCAGAGTGACGCAGCATATGTGGGTGGGTGGGCGGTTATGCTGAGTCAGCCTTGCTTGGACACGGTGGCTTAGT;

[0201] The CD28 aptamers are:

[0202] SEQ ID NO: 168: GGGAGAGAGGAAGAGGGAUGGGGAUUAGACCAUAGGCUCCCAACCCCCCCCGGGAGAGAGGAAGAGGGAUGGGGAUUAGACCAUAGGCUCCCAACCCCCGGG;

[0203] The CD33 aptamers are:

[0204] SEQ ID NO: 169: TACCAGTGCGATGCTCAGCACGCTTATAGGGGCTGGACAAAATTCTACCCAGCCTTT;

[0205] The CD38 aptamer is: SEQ ID NO: 170: TACGTGAATCTCGTACGATACTCTGTAAGCGT;

[0206] The CD44 aptamers are:

[0207] SEQ ID NO: 171: GGGAUGGAUCCAAGCUUACUGGCAUCUGGAUUUGCGGCGUGCCAGAAUAAAGAGUAUAACGUGUGAAUGGGAAGCUUCGAUAGGAAUUCGG;

[0208] The CD105 aptamers are:

[0209] SEQ ID NO: 172: GATCAGTTTTCCATGCCAGTTGGTATTCCGCGACAGTTTGATCTC;

[0210] The CD117 aptamer is: SEQ ID NO: 173: GGGGCCGGGGCAAGGGGGGGGTACCGTGGTAGGAC;

[0211] The CD63 aptamer is: SEQ ID NO: 174: CACCCCACCTCGCTCCCGTGACACTAATGCTA;

[0212] The CD123 aptamers are:

[0213] SEQ ID NO:175: TGCGTGTGTAGTGTGTCTGGGCTACATCGATGAGCTGCCTAGGGTCCCTCTTAGGGATTTGGGCGG;

[0214] The EGFR aptamer is:

[0215] 1) SEQ ID NO:176: GCCTTAGTAACGTGCTTTGATGTCGATTCGACAGGAGGC; or

[0216] 2) SEQ ID NO:177: GCCUUAGUAACGUGCUUUGAUGUCGAUUCGACAGGAGGC; or

[0217] 3) SEQ ID NO:178: UGCCGCUAUAAUGCACGGAUUUAAUCGCCGUAGAAAAGCAUGUCAAAGCCGUU; [[ID=1​​​​​​​​​​​​​​​​​​​​​​​​​​​​3) SEQ ID NO: 185: GGGAAACUAGGGCGUUAACGUGACCAGUGUUUCCC;

[0228] The FGF5 aptamers are:

[0229] SEQ ID NO: 186: GGGCGACCUCUCCGUACUGACCUACAGAGCGACAUACUAGUGUAUCCAGAUCGCCC;

[0230] The FAP aptamer is: 1) SEQ ID NO: 187: TGGGGGTTGAGGCTAAGCCGA; or

[0231] 2) SEQ ID NO: 188: CCGCTCGAGCTAGTCTGACAAAGAGAAACAC;

[0232] The GPC1 aptamer is: SEQ ID NO: 189: AACGGAGTGTGGCTAACTCGA;

[0233] The GPC3 aptamer is: SEQ ID NO: 190: TAACGCTGACCTTAGCTGCATGGCTTTACATGTTCCA;

[0234] The GSK836 aptamer is: SEQ ID NO: 191: GCAGAGGTGAAGCGAAGTCG;

[0235] HBsAg aptamers are:

[0236] SEQ ID NO: 192: CACAGCGAACAGCGGCGGACATAATAGTGCTTACTACGAC;

[0237] The Her2 aptamers are:

[0238] 1) SEQ ID NO: 193: AGCCGCGAGGGGAGGGATAGGGTAGGGCGCGGCT; or

[0239] 2) SEQ ID NO: 194: AGCCGCGAGGGGAGGGAUAGGGUAGGGCGCGGCU;

[0240] The Her3 aptamers are:

[0241] 1) SEQ ID NO: 195: GGGAGCTCAGAATAAACGCTCAAAGGGTCAAGCTGATTACACTTTGTCCACTATTGGGTCCTTCGACATGAGGCCCGGATC; or

[0242] 2) SEQ ID NO: 196: GGGAGCTCAGAATAAACGCTCAAGGCTAACAGCACGCAACGGGGGGGAGTAATCGTGTCTGTTCGACATGAGGCCCGGATC; or

[0243] 3) SEQ ID NO: 197: CAGCGAAAGUUGCGUAUGGGUCACAUCGCAGGCACAUGUCAUCUGGGCG; or

[0244] 4) SEQ ID NO: 198: GAAUUCCGCGUGUGCCAGCGAAAGUUGCGUAUGGGCCACAUCGCAGGCACAUGUCAUCUGGGCGGUCCGUUCGGGAUCC;

[0245] The HMGA2-aptamer is: SEQ ID NO: 199: GGAAAAAATTTTTTAAAAAACCC;

[0246] The H2 aptamers are:

[0247] SEQ ID NO: 200:

[0248] GGGCCGTCGAACACGAGCATGGTGCGTGGACCTAGGATGACCTGAGTACTGTCC;

[0249] IFN-γ aptamers are:

[0250] SEQ ID NO:201: CCGCCCAAATCCCTAAGAGAAGACTGTAATGACATCAAACCAGACACACACACTACACACGCA;

[0251] The IL-4Ra aptamer (also known as the CD124 aptamer) is:

[0252] 1) SEQ ID NO: 202: GGAGGACGAUGCGGAAAAAGCAACAGGGUGCUCCAUGCGCAUGGAACCUGCGCGCAGACGACUCGCUGAGGAUCCGAGA; or

[0253] 2) SEQ ID NO: 203: AAAAAGCAACAGGGUGCUCCAUGCGCAUGGAACCUGCGCG;

[0254] IL-17 aptamer:

[0255] 1) SEQ ID NO: 204: CTTGGATCACCATAGTCGCTAGTCGAGGCT; or

[0256] 2)SEQ ID NO:205:GCGGCATCCTATCACGCATTGACC

[0257] The LAG-3 aptamers are:

[0258] SEQ ID NO: 206: GGGAGAGAGAUAUAAGGGCCUCCUGAUACCCGCUGCUAUCUGGACCGAUCCCAUUACCAAAUUCUCUCCC;

[0259] The LZH8 aptamer is:

[0260] SEQ ID NO:207:ATCCAGAGTGACGCAGCATATTAGTACGGCTTAACCCCATGGTGGACACGGTGGCTTAGT;

[0261] The MUC1 aptamer is:

[0262] 1) SEQ ID NO: 208: GCAGTTGATCCTTTGGATACCCTGG; or

[0263] 2) SEQ ID NO: 209: GAAGTGAAAATGACAGAACACAACA; or

[0264] 3) SEQ ID NO: 210: AACCGCCCAAATCTCTAAGAGTCGGACTGCAACCTATGCTATCGTTGATGTCTGTCCAAGCAACACAGACACACTACACACACGCACA; or

[0265] 4) SEQ ID NO: 211: AATGACAGAACACAACATT; or

[0266] 5) SEQ ID NO: 212: GCAGUUGAUCCUUUGGAUACCCUGG;

[0267] The M5 aptamer is:

[0268] SEQ ID NO: 213: AGCAGCACAGAGGTCAGATGCTTGGTTCCACCGTACTGACTGTAGTAAAATCTGATCACTCCTATGCGTGCTACCGTGAA;

[0269] The M7 aptamer is:

[0270] SEQ ID NO: 214: AGCAGCACAGAGGTCAGATGTAGTCGGTCTTCTTGTTTGAAACTGCTAATTTTGAAAAAACCTATGCGTGCTACCGTGAA;

[0271] The M1 aptamer is:

[0272] SEQ ID NO: 215: AGCAGCACAGAGGTCAGATGATATAACCTTAATAAATAAAATATAAATTATTTAATCTTACCTATGCGTGCTACCGTGAA;

[0273] The MRP1 aptamers are:

[0274] SEQ ID NO: 216: GGGAGAAUAGUCAACAAAUCGUUUGGGGCGACUUCUCCUUCCUUUCUCCC;

[0275] The N5 aptamer is: SEQ ID NO: 217: GATTGAGTAGATAGTGGTTCTGTACGTAGTGAAAGAGTGG;

[0276] The NG-Dua aptamer is:

[0277] SEQ ID NO: 218: CAAGTTGCTCGTCCGATACGTTTGGTTGGTGTGGTTGGCAGTATCGCAGGTCCAAGTTGCTCGTCCGATACAACGGAGTGTGGCTAACTCGA;

[0278] The aptamer for NKG2D_#-20-N-15 is:

[0279] SEQ ID NO: 219: CAAGTTGCTCGTCGCGATACGTTTTGGTTGGTGTGGTTGGCAGTATC;

[0280] The NSE aptamer is: SEQ ID NO: 220: TCACACGGACCTCTCTCTACATTAATTGCGCATTTCGTT;

[0281] The SARS-CoV-2-N15 aptamers are:

[0282] SEQ ID NO: 221: GCTGGATGTTCATGCTGGCAAAATTCCTTAGGGGCACCGTTACTTTGACACATCCAGC;

[0283] The SARS-CoV-2-N48 aptamers are:

[0284] SEQ ID NO: 222: GCTGGATGTCGCTTACGACAATATTCCTTAGGGGCACCGCTACATTGACACATCCAGC;

[0285] The SARS-CoV-2-N58 aptamers are:

[0286] SEQ ID NO: 223: GCTGGATGTCACCGGATTGTCGGACATCGGATTGTCTGAGTCATATGACACATCCAGC;

[0287] The SARS-CoV-2-N61 aptamers are:

[0288] SEQ ID NO: 224: GCTGGATGTTGACCTTTACAGATCGGATTCTGTGGGGCGTTAAACTGACACATCCAGC;

[0289] The OX40 aptamers are:

[0290] 1) SEQ ID NO: 225: GGGAGGACGATGCGGCAGTCTGCATCGTAGGAATCGCCACCGTATACTTTCCCACCAGACGACTCGCTGAGGATCCGAGA;

[0291] 2) SEQ ID NO: 226: GGGAGGACGAUGCGGCAGUCUGCAUCGUAGGAAUCGCCACCGUAUACUUUCCCACCAGACGACUCGCUGAGGAUCCGAGA;

[0292] 3) SEQ ID NO: 227: CAGTCTGCATCGTAGGATTAGCCACCGUATCTTTCCCAC;

[0293] 4) SEQ ID NO:228: GGGAGGACGAUGCGGCAGUCUGCAUCGUAGGAAUCGCCACCGUAUACUUUCCCACCAGACGACUCGCUG;

[0294] 5) SEQ ID NO:229: CAGUCUGCAUCGUAGGAAUCGCCACCGUAUACUUUCCCAC;

[0295] 6) SEQ ID NO:230: GGGAUGCGGAAAAAAGAACACUUCCGAUUAGGGCCCACCCUAACGGCCGCAGAC;

[0296] The PSMA aptamer is:

[0297] 1) SEQ ID NO:231: GGGAGGACGATGCGGATCAGCCATGTTTACGTCACTCCT; or

[0298] 2) SEQ ID NO:232: GCGTTTTCGCTTTTGCGTTTTGGGTCATCTGCTTACGATAGCAATGCT; or

[0299] 3) SEQ ID NO:233: GGGAGGACGAUGCGGAUCAGCCAUGUUUACGUCACUCCU; or

[0300] 4) SEQ ID NO:234: GGGACCGAAAAAGACCUGACUUCUAUACUAAGUCUACGUUCCC;

[0301] The PDGFRβ aptamer is:

[0302] 1) SEQ ID NO:235: TGTCGTGGGGCATCGAGTAAATGCAATTCGACA; or

[0303] 2) SEQ ID NO:236: UGUCGUGGGGCAUCGAGUAAAUGCAAUUCGACA;

[0304] The PDGF aptamer is:

[0305] SEQ ID NO:237: CAGGCTACGGCACGTAGAGCATCACCATGATCCTG;

[0306] The aptamers of PD-L1 are selected from any one or more of the following:

[0307] 1) SEQ ID NO:238: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGG;

[0308] 2) SEQ ID NO:239: GCCCCAGTTATGCTTTCCCCCTCTGTCTCTTTG;

[0309] 3) SEQ ID NO:240: ATCGCCCGCAGCACCCATTTGTTTTTTTTTG;

[0310] 4) SEQ ID NO:241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT;

[0311] 5) SEQ ID NO:242: TGCCCGCACATCAACTCATTGATAGACAATGCGTCCACTCGGGCA;

[0312] 6) SEQ ID NO:243: TGCCCGCACATCAACTCATTGATAGACAATGCGTCCACTACGGGC;

[0313] 7) SEQ ID NO:244: CGGGCACACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT;

[0314] 8) SEQ ID NO:245: GTTGGTCACATCAACTCATTGATAGACAATGCGTCCACTACCAAC;

[0315] 9) SEQ ID NO:246: GGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCC;​​​​​​​​12) SEQ ID NO: 249: CTACGAGACGAACTTATGCGTAATAATGACTGTCGTAG;

[0319] The PD1 aptamer is selected from any one or more of the following:

[0320] 1) SEQ ID NO: 250: GACGATAGCGGTGACGGCACAGACGGTACAGTTCCCGTCCCTGCACTACACGTATGCCCGCTTCCGTCCGTCGCTC;

[0321] 2) SEQ ID NO: 251: GAGCGACGGACGGAAGCGGCATACGTGTAGTGCAGGGACGGGAACTGTACCGTCTGTGCCGTCACCGCTATCGTC;

[0322] 3) SEQ ID NO: 252: GGATCCTATGACGCATTGACCCGCTGCCTCTACTGAGGCTGTGTCAGTGTGCGGCTCGGACTGTTGAATTC;

[0323] 4) SEQ ID NO: 253: AGCGGTGACGGCACAGACGGTACAGTTCCCGTCCCTGCACTACACGTATGCCGCT;

[0324] 5) SEQ ID NO: 254: ACCGACAGTGAAGGACTCAGCGAACTCTCAGACTCGGTTC;

[0325] The PTK-7 aptamer is:

[0326] SEQ ID NO:255: ATCTAACTGCTGCGCCGCCGGGAAAATACTGTACGGTTAGA;

[0327] The ProGRP-48 aptamers are:

[0328] SEQ ID NO:256: CATGCGGAGTAGAGCGAGCCCAGATAGTCCCTGGTTATTTCCTTAGG;

[0329] SF aptamers are:

[0330] SEQ ID NO: 257: GATCTCTCTCTGCCCTAAGTCCGCACCCGTGCTTCCCTGT;

[0331] The TBA15 aptamer is: SEQ ID NO: 258: GGTTGGTGTGGTTGG;

[0332] The TBA29 aptamer is: SEQ ID NO: 259: AGTCCGTGGTAGGGCAGGTTGGGGTGACT;

[0333] The TFRA4 aptamer is: SEQ ID NO: 260: GCGTGGTACCACGC or SEQ ID NO: 261: GCGUGGUACCACGC;

[0334] The TFRA3 aptamers are:

[0335] 1) SEQ ID NO: 262: GCGTGGTCACACGC; or

[0336] 2) SEQ ID NO: 263: GCGUGGUCACACGC; or

[0337] 3) SEQ ID NO: 264: GCGGCGCCCACGAGCGTTCGCGTGGTCACACGCGTTCCCGCCCTCCTACATAGGGCGCATAGCCGTGGGCGCCGC;

[0338] The TTA1 aptamer is:

[0339] SEQ ID NO:265: CCTGCACTTGGCTTGGATTTCAGAAGGGAGACCC; or

[0340] SEQ ID NO:267: CCUGCACUUGGCTTGGAUUUCAGAAGGGAGACCC;

[0341] The TLS9a aptamers are:

[0342] SEQ ID NO:268: AGTCCATTTTTATTCCTGAATATTTGTTAACCTCATGGAC;

[0343] TGF-β aptamers are:

[0344] SEQ ID NO: 269: ACATTGCTGCGTGATCGCCTCACATGGGTTTGTCTGGTCGATTTGGAGGTGGTGGGTGGC;

[0345] The TIM3 aptamers are:

[0346] SEQ ID NO: 270: GGGAGAGGACCAGUA-GCCACUAUGGUGUUGGAGCUAGCGG-CAGAGCGUCGCGGUCCUCCC; or

[0347] SEQ ID NO: 271: GGGAGAGGACCAGUA-CUGGUAGUUCUCUGUGCGGACUCCUA-CAGAGCGUCGCGGUCCUCCC;

[0348] The TIMC-d aptamer is:

[0349] SEQ ID NO:272: AAGCAACACUUAGUCGCGAUUGAUACGUGCGCAGUCAU;

[0350] The TIMC-11 aptamer is:

[0351] SEQ ID NO: 273: GGAGGACGAUGCGGGGAAGCAACACUUAGUCGCGAUUGAUACGUGCGCAGUCAUCAGACGACUCGCUGAGGAUCCGAGA;

[0352] The TNF-α aptamer is: SEQ ID NO: 274: GCGGCCGATAAGGTCTTTCCAAGCGAACGAAAA;

[0353] The TNF aptamer is: SEQ ID NO: 275: GCGCCACTACAGGGGAGCTGCCATTCGAATAGGTGGGCCGC;

[0354] The T1 aptamer is:

[0355] SEQ ID NO:276: CGCTCGATAGATCGAGCTTCGCTCGATGTGGTGTTGTGGGGGCTTGTATTGGTCGATCACGCTCTAGAGCACTG;

[0356] The sequence of the Vap7 aptamer is: SEQ ID NO: 277: TGGTGGGGGTGGACGGGCCGGGTAGA;

[0357] The VEGF aptamers are:

[0358] SEQ ID NO: 278: AUGCAGUUUGAGAAGUCGCGCAU; or SEQ ID NO: 279: GGTGGGGGTGGACGGGCCGGGTAGA;

[0359] The VEGF165 aptamer is: SEQ ID NO: 280: CGGAAUCAGUGAAUGCUUAUACAUCCG;

[0360] The VEGF121 aptamer is: SEQ ID NO: 281: TGTGGGGGTGGACTGGGTGGGTACC;

[0361] The VEGF-V7t1 aptamer is: SEQ ID NO: 282: TGTGGGGGTGGACGGGCCGGGTAGA;

[0362] The VCAM-1 aptamer is:

[0363] SEQ ID NO: 283: ATACCAGCTTATTCAATTGGACACGGCAAAGGGGTATAGCCTACCGGACCGTGAACATGGAATGGTGTGCTGCGTGGAGATAGTAAGTGCAATCT; or

[0364] SEQ ID NO: 284: GGACACGGCAAAGGGGTATAGCCTACCGGACCGTGAACATGGAATGGTGTGCTGCGTGG;

[0365] The VCAM-12d aptamer is:

[0366] SEQ ID NO: 285: AGGGAATCTTGCCTAGGGAGGGAGTAGCGAAAGGGCTCA;

[0367] The 4-1BB aptamer is:

[0368] SEQ ID NO: 286: GGGAGAGAGGAAGAGGGAUGGGCGACCGAACGUGCCCUUCAAAGCCGUUCACUAACCAGUGGCAUAACCCAGAGGUCGAUAGUACUGGAUCCCCCC;

[0369] The PL-45 aptamers are:

[0370] SEQ ID NO: 287: ACTCATAGGGTTAGGGGCTGCTGGCCAGATACTCAGATGGTAGGGTTACTATGAGC;

[0371] The EP166 aptamer is:

[0372] SEQ ID NO: 288: AACAGAGGGACAAACGGGGGAAGATTTGACGTCGACGACA;

[0373] The AGC aptamers are:

[0374] SEQ ID NO: 289: CGACCCGGCACAAACCCAGAACCATATACACGATCATTAGTCTCCTGGGCCG;

[0375] The Karpas299 aptamers are:

[0376] SEQ ID NO:290: ATCCAGAGTGACGCAGCACCACCACCGTACAATTTTTTCATTACCTACTCGGC;

[0377] The SW620 aptamer is:

[0378] SEQ ID NO: 291: CCCATCAATGTTACGACCCGCTAGGGCTGCTGTGCCATCGGGTAA;

[0379] The MDA-MB-231 aptamer is:

[0380] SEQ ID NO: 292: AGAATTCAGTCGGACAGCGAAGTAGTTTTCCTTCTAACCTAAGAACCCGCGGCAGTTTAATGTAGATGGACGAA;

[0381] The MCF-7 aptamer is:

[0382] SEQ ID NO: 293: GCATGGGGTTTCGGCGTTTCGTCTATCTTGTTTCTGTTAGCGTCT;

[0383] The PC-3 aptamer is: SEQ ID NO: 294: TGCCACTACAGCTGGTTCGGTTTGGTGACTTCGTTCTTCGTTGTGGTGCTTAGTGGC.

[0384] Furthermore, the small molecule compound with targeting effect is selected from one or more of folic acid, biotin, vitamin B12 and mannose, and the small molecule compound with targeting effect is located at the 5' end or 3' end of at least one of sequence a, sequence b and sequence c.

[0385] Furthermore, various different oligonucleotide effector molecules are independently mounted on the nucleic acid vector by any one or more of the following methods: 1) a single-stranded bonding bridge sequence; 2) a complementary sequence of the single-stranded bonding bridge sequence; 3) a transition sequence, wherein the single-stranded bonding bridge sequence and the transition sequence are the single-stranded bonding bridge sequence and the transition sequence in the nucleic acid vector of claim 3.

[0386] Furthermore, at least one oligonucleotide effector molecule has a modification on one or more nucleotide molecules, and the modification is selected from at least one of the following: F-type, methyl, amino, disulfide, carbonyl, carboxyl, sulfhydryl, aldehyde, thio, reverse dT and locked nucleic acid.

[0387] Furthermore, the phosphate backbone between the 5' end nucleotides of the antisense strand and the sense strand of the siRNA is thio-modified, and the 3' end has a dTdT modification or UU, or the 3' end of the antisense strand of the siRNA is connected to AA, UU or a combination of any two nucleotides.

[0388] Furthermore, the miRNA has a phosphorothioate modification or a locked nucleic acid modification.

[0389] Furthermore, the nucleic acid aptamer has any one or more of the following modifications: thio, 2'-F or 2'-O-MOE.

[0390] Furthermore, the nucleic acid immunostimulator has a thiolation modification.

[0391] Furthermore, the nucleic acid drug is selected from any one of the following 99 drugs.

[0392] Drug 1): 3*CpG2006-DNA vector, wherein the DNA vector is the 13th group of nucleic acid vectors of the aforementioned 26 backbone sequences, and three CpG2006s are connected to the 5' end of sequence a, sequence b, and sequence c respectively through transition sequences;

[0393] Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides;

[0394] Preferably, the transition sequence is TTTTT.

[0395] Drug 2): 2*CpG1826-2*mannose-DNA vector, wherein the DNA vector is the nucleic acid vector of group 1) among the aforementioned 26 backbone sequences, wherein the two CpG1826s are connected to the 5' end of sequence a and sequence c, respectively, via a transition sequence, and the two mannoses are located at the 5' end and 3' end of sequence b, respectively;

[0396] Preferably, the transition sequence is TTTTT;

[0397] Preferably, the sequence of CpG1826 is: SEQ ID NO: 59: TCCATGACGTTCCTGACG, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides.

[0398] Drug 3): 2*CpG1826-CD40 aptamer-DNA vector, wherein the DNA vector is the nucleic acid vector of group 1) among the aforementioned 26 backbone sequences, two CpG1826s are connected to the 5' end of sequence a and sequence c, respectively, via a transition sequence, and the CD40 aptamer is connected to the 5' end of sequence b via a transition sequence;

[0399] Preferably, the sequence of CpG1826 is: SEQ ID NO: 59: TCCATGACGTTCCTGACG, wherein the phosphate backbone between two adjacent nucleotides is thiolated;

[0400] Preferably, the transition sequence is TTTTT;

[0401] Preferably, the sequence of the CD40 aptamer is SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG.

[0402] Drug 4): 2*CpG2006-CD40 aptamer-DNA vector, wherein the DNA vector is the nucleic acid vector of group 1) among the aforementioned 26 backbone sequences, two CpG2006s are connected to the 5' end of sequence a and sequence c, respectively, via a transition sequence, and the CD40 aptamer is connected to the 5' end of sequence b via a transition sequence;

[0403] Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides;

[0404] Preferably, the transition sequence is TTTTT;

[0405] Preferably, the sequence of the CD40 aptamer is SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG.

[0406] Drug 5): 4*CpG2006-CD40 aptamer-DNA vector, wherein the DNA vector is the nucleic acid vector of group 1) among the aforementioned 26 backbone sequences, two CpG2006s are connected in series to form a CpG2006 doublet, and the two CpG2006 doublets are respectively connected to the 5' end of sequence a and sequence c, and the CD40 aptamer is connected to the 5' end of sequence b via a transition sequence;

[0407] Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides;

[0408] Preferably, the transition sequence is TTTTT;

[0409] Preferably, the sequence of the CD40 aptamer is SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG.

[0410] Drug 6): 2*CpG1826-CD40 aptamer-2*mannose-DNA vector, wherein the DNA vector is the nucleic acid vector of group 1), two CpG1826s are connected to the 5' end of sequence a and sequence c, respectively, via a transition sequence, the CD40 aptamer is connected to the 5' end of sequence b via a transition sequence, and two mannoses are located at the 3' end of sequence b and sequence c, respectively;

[0411] Preferably, the sequence of CpG1826 is: SEQ ID NO: 59: TCCATGACGTTCCTGACG, wherein the phosphate backbone between two adjacent nucleotides is thiolated;

[0412] Preferably, the transition sequence is TTTTT;

[0413] Preferably, the sequence of the CD40 aptamer is SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, and the phosphate backbone between the first three nucleotides at the 5' end is thiolated.

[0414] Drug 7): CpG1826-CD40 aptamer-mannose-MUC1 aptamer-DNA vector, wherein the DNA vector is the nucleic acid vector of group 1) among the aforementioned 26 backbone sequences, CpG1826 is linked to the 5' end of sequence a via a transition sequence, the CD40 aptamer is linked to the 5' end of sequence b via a transition sequence, the MUC1 aptamer is linked to the 5' end of sequence c via a transition sequence, and mannose is located at the 3' end of sequence c;

[0415] Preferably, the sequence of CpG1826 is: SEQ ID NO: 59: TCCATGACGTTCCTGACG, wherein the phosphate backbone between two adjacent nucleotides is thiolated;

[0416] Preferably, the transition sequence is TTTTT;

[0417] Preferably, the sequence of the CD40 aptamer is SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG;

[0418] Preferably, the MUC1 aptamer sequence is: SEQ ID NO: 208: GCAGTTGATCCTTTGGATACCCTGG.

[0419] Drug 8) 2*CpG2006-CD40 aptamer-AmiR-21-3*mannose-DNA vector, wherein the DNA vector is the first group of the aforementioned 26 backbone sequence nucleic acid vectors, two CpG2006s are connected to the 5' end of sequence a and sequence c, respectively, via a transition sequence, the CD40 aptamer is connected to the 5' end of sequence b via a transition sequence, AmiR-21 is directly connected to the 3' end of sequence b, and three mannoses are connected to the 3' end of sequence a, AmiR-21, and sequence c, respectively;

[0420] Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides;

[0421] Preferably, the transition sequence is TTTTT;

[0422] Preferably, the sequence of the CD40 aptamer is SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG;

[0423] Preferably, the sequence of AmiR-21 is GATAAGCT, wherein each position is a locked nucleic acid modification.

[0424] Drug 9): 2*CpG2006-CD40 aptamer-CD16a aptamer-CTLA-4 aptamer-DNA vector, wherein the DNA vector is the second group of nucleic acid vectors of the aforementioned 26 backbone sequences, wherein the two CpG2006s are connected to the 5' end of sequence a and sequence c, respectively, via a transition sequence, the CD40 aptamer is connected to the 3' end of sequence b via a transition sequence, the CD16a aptamer is connected to the 5' end of sequence b via a transition sequence, and the CTLA-4 aptamer is connected to the 3' end of sequence c via a transition sequence;

[0425] Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides;

[0426] Preferably, the transition sequence is TTTTT;

[0427] Preferably, the sequence of the CD16a aptamer is:

[0428] SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, with thiolation modification between the first two positions of the 5' end;

[0429] Preferably, the sequence of the CD40 aptamer is:

[0430] SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the phosphate backbone between the last two nucleotides at the 3' end is thiolated;

[0431] Preferably, the sequence of the CTLA-4 aptamer is:

[0432] SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU, a thiolation modification exists in the phosphate backbone between the second and third nucleotides from the 3' end.

[0433] Drug 10): 2*CpG2006-CTLA-4 aptamer-PD-L1 aptamer-DNA vector, wherein the DNA vector is the nucleic acid vector of group 3) among the aforementioned 26 backbone sequences, two CpG2006s are linked in series to form a CpG2006 doublet, the CpG2006 doublet is connected to the 5' end of sequence a via a transition sequence, the PD-L1 aptamer is connected to the 5' end of sequence c via a transition sequence, and the CTLA-4 aptamer is connected to the 5' end of sequence b via a transition sequence;

[0434] Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides;

[0435] Preferably, the sequence of the PD-L1 aptamer is:

[0436] SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0437] Preferably, the sequence of the CTLA-4 aptamer is:

[0438] SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0439] Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides;

[0440] Preferably, the transition sequence is TTTTT.

[0441] Drug 11): CpG2006-CD40 aptamer-PD-L1 aptamer-DNA vector, selected from any of the following structures:

[0442] i) CCPD3: The DNA vector is group 12 of the aforementioned 26 backbone sequence nucleic acid vectors, with CpG2006 linked to the 5' end of sequence a via a transition sequence, the PD-L1 aptamer linked to the 5' end of sequence c via a transition sequence, and the CD40 aptamer linked to the 5' end of sequence b via a transition sequence. In this DNA vector, the phosphate backbone between the first three nucleotides at the 3' end of sequence a, the 3' end of sequence b, and the 3' end of sequence c is thiolated.

[0443] Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides;

[0444] Preferably, the sequence of the PD-L1 aptamer is:

[0445] SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, the phosphate backbone between the first three adjacent nucleotides at the 5' end is thiolated;

[0446] Preferably, the sequence of the CD40 aptamer is:

[0447] SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the phosphate backbone between the first three adjacent nucleotides at the 5' end is thiolated;

[0448] Preferably, the transition sequence is TTTTT;

[0449] or

[0450] ii) CCPD3 variant 1: The DNA vector is the nucleic acid vector of group 12 among the aforementioned 26 backbone sequences, wherein CpG2006 is linked to the 5' end of sequence a via the transition sequence TTTTT, and the CD40 aptamer is linked to the 5' end of sequence b via the transition sequence TTTTT; the PD-L1 aptamer is linked to the 5' end of sequence c via the transition sequence ATTT. In the DNA vector, the phosphate backbone between the first two nucleotides at the 3' end of sequence a, the 3' end of sequence b, and the 3' end of sequence c is thiolated.

[0451] Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides;

[0452] Preferably, the sequence of the CD40 aptamer is:

[0453] SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the phosphate backbone between the first three adjacent nucleotides at the 5' end is thiolated;

[0454] Preferably, the sequence of the PD-L1 aptamer is:

[0455] SEQ ID NO: 238: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGG, the phosphate backbone between the first four adjacent nucleotides at the 5' end is thiolated;

[0456] or

[0457] iii) CCPD3 variant 2: The sequence of the DNA vector is:

[0458] a Sequence: SEQ ID NO: 295: GCCCACGAGCGTTCCGGGAGA;

[0459] b sequence: SEQ ID NO: 49: TCTCCCGGTTCGCCGCGAG;

[0460] c sequence: SEQ ID NO: 296: CTCGCGGCCATAGCCGTGGGC;

[0461] CpG2006 is connected to the 5' end of sequence a through the transition sequence TTTT, the CD40 aptamer is connected to the 5' end of sequence b through the transition sequence TTTT, and the PD-L1 aptamer is connected to the 5' end of sequence c through the transition sequence TTTT.

[0462] Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides;

[0463] Preferably, the sequence of the CD40 aptamer is:

[0464] SEQ ID NO: 156: GCCAACGAGTAGGCGATAGCGCGTGGC, the phosphate backbone between the first four adjacent nucleotides at the 5' end is thiolated;

[0465] Preferably, the sequence of the PD-L1 aptamer is:

[0466] SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, the phosphate backbone between the first five adjacent nucleotides at the 5' end is thiolated;

[0467] or

[0468] iv) CCPD3 variant 3: The sequence of the DNA vector is:

[0469] a Sequence: SEQ ID NO: 295: GCCCACGAGCGTTCCGGGAGA;

[0470] b sequence: SEQ ID NO: 49: TCTCCCGGTTCGCCGCGAG;

[0471] c sequence: SEQ ID NO: 296: CTCGCGGCCATAGCCGTGGGC;

[0472] CpG2006 is connected to the 5' end of sequence a through the transition sequence TTTT, the CD40 aptamer is connected to the 5' end of sequence b through the transition sequence TTTT, and the PD-L1 aptamer is connected to the 5' end of sequence c through the transition sequence TTTT.

[0473] Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides;

[0474] Preferably, the sequence of the CD40 aptamer is:

[0475] SEQ ID NO: 156: GCCAACGAGTAGGCGATAGCGCGTGGC, the phosphate backbone between the first four adjacent nucleotides at the 5' end is thiolated;

[0476] Preferably, the sequence of the PD-L1 aptamer is:

[0477] SEQ ID NO: 246: GGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCC, the phosphate backbone between the first four adjacent nucleotides at the 5' end is thiolated;

[0478] v) CCPD3 variant 4:

[0479] The sequence of the DNA vector is:

[0480] a Sequence: SEQ ID NO: 295: GCCCACGAGCGTTCCGGGAGA;

[0481] b sequence: SEQ ID NO: 49: TCTCCCGGTTCGCCGCGAG;

[0482] c sequence: SEQ ID NO: 296: CTCGCGGCCATAGCCGTGGGC;

[0483] CpG2006 is connected to the 5' end of sequence a through the transition sequence TTTT, the CD40 aptamer is connected to the 5' end of sequence b through the transition sequence TTTT, and the PD-L1 aptamer is connected to the 5' end of sequence c through the transition sequence TTTT.

[0484] Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides;

[0485] Preferably, the sequence of the CD40 aptamer is:

[0486] SEQ ID NO: 156: GCCAACGAGTAGGCGATAGCGCGTGGC, the phosphate backbone between the first four adjacent nucleotides at the 5' end is thiolated;

[0487] Preferably, the sequence of the PD-L1 aptamer is:

[0488] SEQ ID NO: 248: TACAGGTTCTGGGGGGTGGGTGGGGAACCTGTT, the phosphate backbone between the first four adjacent nucleotides at the 5' end is thiolated;

[0489] vi) CCPD3 variant 5:

[0490] The sequence of the DNA vector is:

[0491] a Sequence: SEQ ID NO: 18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC;

[0492] b Sequence: SEQ ID NO: 19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG;

[0493] c sequence: SEQ ID NO: 20: CAGCAGCAGCAGCACGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, wherein SEQ ID NO: 12: CAGCAGCAGCAGCA is a single-stranded connecting bridge sequence;

[0494] CpG2006 is connected to the 5' end of sequence a through the transition sequence TTTT, the CD40 aptamer is connected to the 5' end of sequence b through the transition sequence TTTTT, and the PD-L1 aptamer is connected to the 3' end of the complementary sequence of the single-stranded bridge sequence through the transition sequence TTTTT, and is connected to the 5' end of sequence c through the complementary pairing of the single-stranded bridge sequence and its complementary sequence;

[0495] Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides;

[0496] Preferably, the sequence of the CD40 aptamer is:

[0497] SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the phosphate backbone between the first five adjacent nucleotides at the 5' end is thiolated;

[0498] Preferably, the sequence of the complementary sequence of the single-stranded connecting bridge sequence - the PD-L1 aptamer is: SEQ ID NO: 297: TGCTGCTGCTGCTGTTTTTACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, wherein the phosphate backbone between the first four adjacent nucleotides at the 3' end is thio-modified, wherein SEQ ID NO: 11: TGCTGCTGCTGCTG is the complementary sequence of the single-stranded connecting bridge sequence;

[0499] vii) CCPD3 variant 6:

[0500] The sequence of the DNA vector is:

[0501] a Sequence: SEQ ID NO: 18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC;

[0502] b Sequence: SEQ ID NO: 19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG;

[0503] c sequence: SEQ ID NO: 20: CAGCAGCAGCAGCACGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, wherein SEQ ID NO: 12: CAGCAGCAGCAGCA is a single-stranded connecting bridge sequence;

[0504] CpG2006 is connected to the 5' end of sequence a through the transition sequence TTTT, the CD40 aptamer is connected to the 5' end of sequence b through the transition sequence TTTTT, and the PD-L1 aptamer is connected to the 3' end of the complementary sequence of the single-stranded bridge sequence through the transition sequence TTTTT, and is connected to the 5' end of sequence c through the complementary pairing of the single-stranded bridge sequence and its complementary sequence;

[0505] Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides;

[0506] Preferably, the sequence of the CD40 aptamer is:

[0507] SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the phosphate backbone between the first five adjacent nucleotides at the 5' end is thiolated;

[0508] Preferably, the sequence of the complementary sequence of the single-stranded connecting bridge sequence - TTTTT-PD-L1 aptamer is:

[0509] SEQ ID NO: 298: TGCTGCTGCTGCTGTTTTTTACAGGTTCTGGGGGGTGGGTGGGGAACCTGTT, wherein the phosphate backbone between the first four adjacent nucleotides at the 3' end is thio-modified, wherein SEQ ID NO: 11: TGCTGCTGCTGCTG is the complementary sequence of the single-stranded connecting bridge sequence;

[0510] viii) CCPD3 variant 7:

[0511] The sequence of the DNA vector is:

[0512] a sequence: SEQ ID NO: 15: GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC, wherein SEQ ID NO: 7: TGTAGCACGGTGGC is the single-stranded connecting bridge sequence A;

[0513] b sequence: SEQ ID NO: 16: CCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, wherein SEQ ID NO: 9: TCGGCGCGGCCGTG is the single-stranded connecting bridge sequence B;

[0514] c sequence: SEQ ID NO: 17: GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG, wherein SEQ ID NO: 11: TGCTGCTGCTGCTG is a single-stranded connecting bridge sequence C;

[0515] CpG2006 is connected to the 5' end of the complementary sequence C' of the single-stranded bridge C sequence through a transition sequence, and CpG2006 is connected to the 3' end of the c sequence through complementary pairing between the complementary sequence C' and the single-stranded bridge C sequence;

[0516] The PD-L1 aptamer is sequentially connected to the transition sequence and the complementary sequence B' of the single-stranded bridge sequence B. The PD-L1 aptamer is connected to the 3' end of the b sequence through the complementary pairing of the complementary sequence B' and the single-stranded bridge sequence B.

[0517] The CD40 aptamer is sequentially connected to the transition sequence and the complementary sequence A' of the single-stranded bridge sequence A. The CD40 aptamer is connected to the 3' end of the a sequence through the complementary pairing of the complementary sequence A' and the single-stranded bridge sequence A.

[0518] Preferably, the sequence of CpG2006 is: SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, wherein the phosphate backbone between adjacent nucleotides is thio-modified;

[0519] Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 156: GCCAACGAGTAGGCGATAGCGCGTGGC, wherein the phosphate backbone between the first four adjacent nucleotides at the 5' end is thiolated;

[0520] Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, wherein the phosphate backbone between the first four adjacent nucleotides at the 5' end is thiolated;

[0521] Preferably, the transition sequence is TTTTT.

[0522] iv) CCPD3-variant 8,

[0523] a sequence is: SEQ ID NO: 18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC;

[0524] b sequence is: SEQ ID NO: 19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG;

[0525] c sequence is: SEQ ID NO: 31: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGC;

[0526] CpG2006 is connected to the 5' end of sequence a through a transition sequence, the CD40 aptamer is connected to the 5' end of sequence b through a transition sequence, and the PD-L1 aptamer is connected to the 5' end of sequence c through the transition sequence shown.

[0527] Preferably, the sequence of CpG2006 is: SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, wherein the phosphate backbone between adjacent nucleotides is thio-modified;

[0528] Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 156: GCCAACGAGTAGGCGATAGCGCGTGGC, wherein the ribose of the first four nucleotides at the 5' end has a 2'-O-MOE modification, and the base of the nucleotide corresponding to Cm has a 5-methyl modification;

[0529] Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, wherein the ribose of the first four nucleotides at the 5' end has a 2'-O-MOE modification, and the base of the nucleotide corresponding to Cm has a 5-methyl modification;

[0530] Preferably, the transition sequence is TTTTT.

[0531] v) CCPD3-Variant 9,

[0532] a sequence is: SEQ ID NO: 18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC;

[0533] b sequence is: SEQ ID NO: 19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG;

[0534] c sequence is: SEQ ID NO: 31: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGC;

[0535] CpG2006 is connected to the 5' end of sequence a through a transition sequence, the CD40 aptamer is connected to the 5' end of sequence b through a transition sequence, and the PD-L1 aptamer is connected to the 5' end of sequence c through the transition sequence shown.

[0536] Preferably, the sequence of CpG2006 is: SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, wherein the phosphate backbone between adjacent nucleotides is thio-modified;

[0537] Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, wherein the ribose of the first five nucleotides at the 5' end has a 2'-O-MOE modification, and the bases of the three nucleotides corresponding to Cm have a 5-methyl modification;

[0538] Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, wherein the ribose of the first five nucleotides at the 5' end has a 2'-O-MOE modification, and the base of the nucleotide corresponding to one Cm has a 5-methyl modification;

[0539] Preferably, the transition sequence is TTTTT.

[0540] vi) CCPD3-Variant 10,

[0541] a sequence is: SEQ ID NO: 18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC;

[0542] b sequence is: SEQ ID NO: 19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG;

[0543] c sequence is: SEQ ID NO: 31: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGC;

[0544] CpG2006 is connected to the 5' end of sequence a through a transition sequence, the CD40 aptamer is connected to the 5' end of sequence b through a transition sequence, and the PD-L1 aptamer is connected to the 5' end of sequence c through the transition sequence shown.

[0545] Preferably, the sequence of CpG2006 is: SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, wherein the phosphate backbone between adjacent nucleotides is thio-modified;

[0546] Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, wherein the ribose of the first five nucleotides at the 5' end has a 2'-O-MOE modification, and the bases of the three nucleotides corresponding to Cm have a 5-methyl modification;

[0547] Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 249: CTACGAGACGAACTTATGCGTAATAATGACTGTCGTAG, wherein the ribose of the first five nucleotides at the 5' end has a 2'-O-MOE modification, and the base of the nucleotide corresponding to one Cm has a 5-methyl modification;

[0548] Preferably, the transition sequence is TTTTT.

[0549] vii) CCPD3-Variant 11,

[0550] a sequence is: SEQ ID NO: 18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC;

[0551] b sequence is: SEQ ID NO: 19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG;

[0552] c sequence: SEQ ID NO: 299: CGCGGCTCGCGGCTCGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the underlined portion is the connecting bridge sequence;

[0553] CpG2006 is connected to the 5' end of sequence a through a transition sequence, the CD40 aptamer is connected to the 5' end of sequence b through a transition sequence, and the PD-L1 aptamer is connected to the 3' end of the complementary sequence of the connecting bridge sequence (SEQ ID NO: 14: AGCCGCGAGCCGCG) and connected to the 5' end of sequence c through the complementary sequence of the connecting bridge sequence and the complementary sequence of the connecting bridge sequence.

[0554] Preferably, the sequence of CpG2006 is: SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, wherein the phosphate backbone between adjacent nucleotides is thio-modified;

[0555] Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, with 2'-O-MOE modification on the ribose of the first five nucleotides at the 5' end;

[0556] Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, with a 2'-O-MOE modification on the ribose of the first 1-5 nucleotides at the 3' end;

[0557] Preferably, the transition sequence is TTTTT.

[0558] viii) CCPD3-Variant 12,

[0559] a sequence is: SEQ ID NO: 18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC;

[0560] b sequence is: SEQ ID NO: 19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG;

[0561] c sequence: SEQ ID NO: 299: CGCGGCTCGCGGCTCGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the underlined portion is the connecting bridge sequence;

[0562] CpG2006 is connected to the 5' end of sequence a through a transition sequence, the CD40 aptamer is connected to the 5' end of sequence b through a transition sequence, and the PD-L1 aptamer is connected to the 3' end of the complementary sequence of the connecting bridge sequence (SEQ ID NO: 14: AGCCGCGAGCCGCG) through a transition sequence, and is connected to the 5' end of sequence c through a complementary pairing between the complementary sequence of the connecting bridge sequence and the connecting bridge sequence.

[0563] Preferably, the sequence of CpG2006 is: SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, wherein the phosphate backbone between adjacent nucleotides is thio-modified;

[0564] Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, with 2'-O-MOE modification on the ribose of the first five nucleotides at the 5' end;

[0565] Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 249: CTACGAGACGAACTTATGCGTAATAATGACTGTCGTAG, with a 2'-O-MOE modification on the ribose of the first 1-5 nucleotides at the 3' end;

[0566] Preferably, the transition sequence is TTTTT.

[0567] Drug 12): CD16a aptamer-CTLA4 aptamer-CpG2006-DNA vector, wherein the DNA vector is group 4) of the aforementioned 26 backbone sequence nucleic acid vectors, the CD16a aptamer is linked to the 5' end of sequence a via a transition sequence, the CTLA-4 aptamer is linked to the 5' end of sequence b via a transition sequence; CpG2006 is linked to the 5' end of sequence c via a transition sequence, and in the DNA vector, the phosphate backbone between the first two nucleotides at the 3' end of sequence a, the 3' end of sequence b, and the 3' end of sequence c is thiolated.

[0568] Preferably, the sequence of the CD16a aptamer is:

[0569] SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0570] Preferably, the sequence of the CTLA-4 aptamer is:

[0571] SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU, the phosphate backbone between the first two nucleotides at the 5' end is thio-modified, C and U are 2'-F modifications, and A and G are 2'-OME modifications;

[0572] Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides;

[0573] Preferably, the transition sequence is TTTTT.

[0574] Drug 13): 2*CpG2006-CD40 aptamer-PD-L1 aptamer-C12 aptamer-DNA vector, wherein the DNA vector is the 5th group of nucleic acid vectors of the aforementioned 26 backbone sequences, wherein the two CpG2006s are connected to the 5' end of sequence a and sequence c, respectively, via transition sequences, and the CD40 aptamer is located at the 5' end of sequence b. In the DNA vector, the phosphate backbone between the first two nucleotides at the 3' end of sequence a, the 3' end of sequence b, and the 3' end of sequence c is thiolated;

[0575] The PD-L1 aptamer is sequentially connected to the transition sequence and the complementary sequence B' of the single-stranded bridge sequence B. The single-stranded bridge sequence B is located at the 3' end of the b sequence. The PD-L1 aptamer is connected to the 3' end of the b sequence through the complementary pairing of the complementary sequence B' and the single-stranded bridge sequence B.

[0576] The C12 aptamer is sequentially connected to the transition sequence and the complementary sequence C' of the single-stranded bridge sequence C. The single-stranded bridge sequence C is located at the 3' end of the c sequence. The C12 aptamer is connected to the 3' end of the c sequence through the complementary pairing between the complementary sequence C' and the single-stranded bridge sequence C.

[0577] Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides;

[0578] Preferably, the transition sequence is TTTTT;

[0579] Preferably, the sequence of the CD40 aptamer is:

[0580] SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the phosphate backbone between the first three adjacent nucleotides at the 5' end is thiolated;

[0581] Preferably, the sequence of the PD-L1 aptamer is:

[0582] SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, the phosphate backbone between the first three adjacent nucleotides at the 5' end is thiolated;

[0583] Preferably, the sequence of the C12 aptamer is:

[0584] SEQ ID NO: 164: GTGGATTGTTGTGTTCTGTTGGTTTTTGTGTTGTC, the phosphate backbone between the first three adjacent nucleotides at the 5' end is thiolated;

[0585] Preferably, the single-stranded connecting bridge sequence B is: SEQ ID NO: 7: TGTAGCACGGTGGC, and the complementary sequence B' is SEQ ID NO: 8: GCCACCGTGCTACA;

[0586] Preferably, the single-stranded connecting bridge sequence C is: SEQ ID NO: 11: TGCTGCTGCTGCTG, and the complementary sequence C' is SEQ ID NO: 12: CAGCAGCAGCAGCA.

[0587] Drug 14): CpG2006-C12 aptamer-CD47 siRNA-PD-L1 aptamer-PD-L1 siRNA-DNA vector, wherein the DNA vector is the sixth group of nucleic acid vectors of the aforementioned 26 backbone sequences, CpG2006 is connected to the 5' end of sequence a through a transition sequence, the C12 aptamer and the antisense strand of CD47 siRNA are connected through a transition sequence, the sense strand of CD47 siRNA is located at the 5' end of sequence b, the antisense strand of CD47 siRNA is complementary to the sense strand of CD47 siRNA, the C12 aptamer and CD47 siRNA are connected to the 5' end of sequence b, the sense strand of PD-L1 siRNA is connected to the 5' end of sequence c, and the PD-L1 aptamer and PD-L1 The antisense strand of the siRNA is connected through a transition sequence, wherein the phosphate backbone between the 3' end of sequence a, the 3' end of sequence b, and the first three nucleotides of the 3' end of sequence c in the DNA vector is thiolated;

[0588] Preferably, the sequence of the C12 aptamer is:

[0589] SEQ ID NO: 164: GTGGATTGTTGTGTTCTGTTGGTTTTTGTGTTGTC, the phosphate backbone between the first three adjacent nucleotides at the 5' end is thiolated;

[0590] Preferably, the antisense strand of the CD47 siRNA is: SEQ ID NO: 79: AUAUCUCUGGGUAAUCACCUU, and the sense strand is: SEQ ID NO: 78: GGUGAUUACCCAGAGAUAUUU, the phosphate backbone between the first three adjacent nucleotides at the 5' end of the antisense strand of the CD47 siRNA is thiolated, the phosphate backbone between the first three adjacent nucleotides at the 5' end of the sense strand of the CD47 siRNA is thiolated, and the phosphate backbone between the first three adjacent nucleotides at the 3' end is thiolated;

[0591] Preferably, the sequence of the PD-L1 aptamer is:

[0592] SEQ ID NO: 239: GCCCCAGTTATGCTTTCCCCCTCTGTCTCTTTG, the phosphate backbone between the first three adjacent nucleotides at the 5' end is thiolated;

[0593] Preferably, the sense strand of the PD-L1 siRNA is: SEQ ID NO: 94: CCAGCACACUGAGAAUCAAUU, and the antisense strand is: SEQ ID NO: 95: UUGAUUCUCAGUGUGCUGGUU. The phosphate backbone between the first three adjacent nucleotides at the 5' end of the sense strand of the PD-L1 siRNA is thiolated, and the phosphate backbone between the first three adjacent nucleotides at the 3' end is thiolated. The phosphate backbone between the first three adjacent nucleotides at the 5' end of the antisense strand of the PD-L1 siRNA is thiolated.

[0594] Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides;

[0595] Preferably, the transition sequence is TTTTT.

[0596] Drug 15): 2*CpG2006-CD40 aptamer-CD16a aptamer-DNA vector, wherein the DNA vector is group 7) of the aforementioned 26 backbone sequence nucleic acid vectors, wherein two CpG2006s are connected to the 5' end of sequence a and sequence c, respectively, via a transition sequence, the CD40 aptamer is connected to the 5' end of sequence b via a transition sequence, and the CD16a aptamer is connected to the 3' end of sequence b via a transition sequence, wherein the phosphate backbone between the first two nucleotides at the 3' end of sequence a and sequence c of the DNA vector is thiolated;

[0597] Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides;

[0598] Preferably, the transition sequence is TTTTT;

[0599] Preferably, the sequence of the CD16a aptamer is:

[0600] SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the phosphate backbone between the first two nucleotides at the 3' end is thiolated;

[0601] Preferably, the sequence of the CD40 aptamer is:

[0602] SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the phosphate backbone between the last two nucleotides at the 5' end is thiolated.

[0603] Drug 16): 2*CpG2006-CD40 aptamer-CD16a aptamer-FAP aptamer-DNA vector, wherein the DNA vector is group 8) of the aforementioned 26 backbone sequence nucleic acid vectors, wherein two CpG2006s are connected to the 5' ends of sequence a and sequence c, respectively, via transition sequences, the CD40 aptamer is connected to the 5' end of sequence b via a transition sequence, the CD16a aptamer is connected to the 3' end of sequence b via a transition sequence, and the FAP aptamer is connected to the 3' end of sequence c via a transition sequence, wherein the phosphate backbone between the first two nucleotides at the 3' end of sequence a of the DNA vector is thiolated;

[0604] Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides;

[0605] Preferably, the transition sequence is TTTTT;

[0606] Preferably, the sequence of the CD16a aptamer is:

[0607] SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the phosphate backbone between the first two nucleotides at the 3' end is thiolated;

[0608] Preferably, the sequence of the CD40 aptamer is:

[0609] SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the phosphate backbone between the last two nucleotides at the 5' end is thiolated;

[0610] Preferably, the sequence of the FAP aptamer is:

[0611] SEQ ID NO: 188: CCGCTCGAGCTAGTCTGACAAAGAGAAACAC, the phosphate backbone between the last two nucleotides at the 3' end is thio-modified.

[0612] Drug 17): 2*CpG2006-VEGF aptamer-CD40 aptamer-PD-L1 aptamer-CD16a aptamer-DNA vector, wherein the DNA vector is the 6th group of nucleic acid vectors of the aforementioned 26 backbone sequences, 2 CpG2006s are connected to the 5' end of sequence a and sequence c, respectively, via a transition sequence, the CD40 aptamer is connected to the 5' end of sequence b via a transition sequence, the PD-L1 aptamer is connected to the 3' end of sequence b via a transition sequence, the CD16a aptamer is connected to the 3' end of sequence c via a transition sequence, and the VEGF aptamer is connected to the 3' end of sequence a via a transition sequence.

[0613] Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides;

[0614] Preferably, the VEGF aptamer:

[0615] SEQ ID NO: 279: GGTGGGGGTGGACGGGCCGGGTAGA, the phosphate backbone between the last two nucleotides at the 3' end is thiolated;

[0616] Preferably, the sequence of the CD40 aptamer is:

[0617] SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0618] Preferably, the sequence of the PD-L1 aptamer is:

[0619] SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, the phosphate backbone between the last two nucleotides at the 3' end is thiolated;

[0620] Preferably, the sequence of the CD16a aptamer is:

[0621] SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the phosphate backbone between the last two nucleotides at the 3' end is thiolated.

[0622] Drug 18): 2*AmiR21-TTA1 aptamer-DNA vector, wherein the DNA vector is the 13th group of nucleic acid vectors of the aforementioned 26 backbone sequences, the two AmiR21s are directly connected to the 5' end of the a sequence and the c sequence, respectively, and the TTA1 aptamer is connected to the 5' end of the b sequence via a transition sequence.

[0623] Preferably, the transition sequence is TTTTT;

[0624] Preferably, the sequence of AmiR21 is GATAAGCT, with each nucleotide having a locked nucleic acid modification;

[0625] Preferably, the sequence of the TTA1 aptamer is:

[0626] SEQ ID NO: 266: CTGCACTTGGCTTGGATTTCAGAAGGGAGACCC.

[0627] Drug 19): 2*AmiR-21-3*Biotin-DNA vector, wherein the DNA vector is the 13th group of nucleic acid vectors of the aforementioned 26 backbone sequences, the two AmiR21s are directly linked to the 5' end of sequence a and sequence c, respectively, and the three biotins are linked to the 5' end and 3' end of sequence b and the 3' end of sequence c, respectively.

[0628] Preferably, the sequence of AmiR-21 is GATAAGCT, wherein each position is a locked nucleic acid modification.

[0629] Drug 20): 2*AmiR-21-4*Biotin-DNA vector, wherein the DNA vector is group 13) of the aforementioned 26 backbone sequence nucleic acid vectors, the two AmiR21s are directly linked to the 5' ends of sequence a and sequence c, respectively, and the four biotins are linked to the 3' end of sequence a, the 5' end and 3' end of sequence b, and the 3' end of sequence c, respectively.

[0630] Preferably, the sequence of AmiR-21 is GATAAGCT, wherein each position is a locked nucleic acid modification.

[0631] Drug 21): 2*AmiR-21-AS1411 aptamer-DNA vector, wherein the DNA vector is the 13th group of nucleic acid vectors of the aforementioned 26 backbone sequences, the two AmiR21s are directly linked to the 5' end of the a sequence and the c sequence, respectively, and the AS1411 aptamer is linked to the 5' end of the b sequence via a transition sequence.

[0632] Preferably, the transition sequence is TTTTT;

[0633] Preferably, the sequence of AmiR-21 is GATAAGCT, wherein each position is a locked nucleic acid modification;

[0634] Preferably, the sequence of the AS1411 aptamer is:

[0635] SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG.

[0636] Drug 22): 2*AmiR-21-AS1411 aptamer-DNA vector, wherein the DNA vector is the 23) group of nucleic acid vectors of the aforementioned 26 backbone sequences, wherein the two AmiR-21s are directly linked to the 5' end of the a sequence and the c sequence, respectively, and the AS1411 aptamer is linked to the 5' end of the b sequence via a transition sequence.

[0637] Preferably, the transition sequence is TTTTT;

[0638] Preferably, the sequence of AmiR-21 is GATAAGCT, wherein positions 1 and 3-5 have 2'-OME modifications, and positions 2 and 6-8 have 2'-F modifications;

[0639] Preferably, the sequence of the AS1411 aptamer is:

[0640] SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG.

[0641] Drug 23): 2*AmiR-21-AS1411 aptamer-biotin-DNA vector, wherein the DNA vector is the nucleic acid vector of group 13) among the aforementioned 26 backbone sequences, the two AmiR-21s are directly linked to the 5' end of sequence a and sequence c, respectively, the AS1411 aptamer is linked to the 5' end of sequence b via a transition sequence, and the biotin is linked to the 3' end of sequence c;

[0642] Preferably, the transition sequence is TTTTT;

[0643] Preferably, the sequence of AmiR-21 is GATAAGCT, wherein each position is a locked nucleic acid modification;

[0644] Preferably, the sequence of the AS1411 aptamer is:

[0645] SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG.

[0646] Drug 24): 2*AmiR-21-CD40 aptamer-DNA vector, wherein the DNA vector is the nucleic acid vector of group 13) among the aforementioned 26 backbone sequences, the two AmiR-21s are directly linked to the 5' end of sequence a and sequence c, respectively, and the CD40 aptamer is linked to the 5' end of sequence b via a transition sequence;

[0647] Preferably, the transition sequence is TTTTT;

[0648] Preferably, the sequence of AmiR-21 is GATAAGCT, wherein each position is a locked nucleic acid modification;

[0649] Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG.

[0650] Drug 25): 2*AmiR-21-MUC1 aptamer-3*biotin-DNA vector, wherein the DNA vector is the nucleic acid vector of group 13) among the aforementioned 26 backbone sequences, the two AmiR21s are directly linked to the 5' end of sequence a and sequence c, respectively, and the MUC1 aptamer is linked to the 5' end of sequence b via a transition sequence;

[0651] Preferably, the transition sequence is TTTTT;

[0652] Preferably, the sequence of AmiR-21 is GATAAGCT, wherein each position is a locked nucleic acid modification;

[0653] Preferably, the sequence of the MUC 1 aptamer is: SEQ ID NO: 208: GCAGTTGATCCTTTGGATACCCTGG.

[0654] Drug 26): AmiR-21-AS1411 aptamer-A15 aptamer-2*biotin-DNA vector, wherein the DNA vector is the nucleic acid vector of group 13) among the aforementioned 26 backbone sequences, AmiR21 is directly linked to the 5' end of sequence a, the AS1411 aptamer and the A15 aptamer are each linked to the 5' end of sequence b and the 5' end of sequence c, respectively, via a transition sequence, and two biotins are linked to the 3' end of sequence b and the 3' end of sequence c, respectively;

[0655] Preferably, the transition sequence is TTTTT;

[0656] Preferably, the sequence of AmiR-21 is GATAAGCT, wherein each position is a locked nucleic acid modification;

[0657] Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG;

[0658] Preferably, the sequence of the A15 aptamer is: SEQ ID NO: 129: CCCTCCTACATAGGG.

[0659] Drug 27): 2*Mannose-2*AmiR-21-DNA vector, wherein the DNA vector is the nucleic acid vector of group 13) among the aforementioned 26 backbone sequences, two mannose groups are respectively linked to the 5' and 3' ends of the b sequence, and two AmiR-21s are directly linked to the 5' ends of the a sequence and the c sequence, respectively;

[0660] Preferably, the sequence of AmiR-21 is GATAAGCT, wherein each position is a locked nucleic acid modification.

[0661] Drug 28): 2*mannose-A15 aptamer-2*AmiR-21-DNA vector, wherein the DNA vector is group 13) of the aforementioned 26 backbone sequence nucleic acid vectors, the A15 aptamer is linked to the 5' end of the b sequence via a transition sequence, two mannose groups are linked to the 5' end of the A15 aptamer and the 3' end of the b sequence, respectively, and the two AmiR-21s are directly linked to the 5' end of the a sequence and the c sequence, respectively;

[0662] Preferably, the sequence of AmiR-21 is GATAAGCT, wherein each position is a locked nucleic acid modification;

[0663] Preferably, the sequence of the A15 aptamer is: SEQ ID NO: 129: CCCTCCTACATAGGG.

[0664] Drug 29): a 2*mannose-survivin siRNA-DNA vector, wherein the DNA vector is the nucleic acid vector of group 13) among the aforementioned 26 backbone sequences, two mannose groups are attached to the 5' and 3' ends of the b sequence, respectively, the sense strand of the survivin siRNA is attached to the 3' end of the c sequence, and the antisense strand of the survivin siRNA is attached to the 3' end of the c strand through complementary pairing with the sense strand of the survivin siRNA;

[0665] Preferably, the positive strand of survivin siRNA is: SEQ ID NO: 104: UGCAGGUUCCUUAUCUGUCATT,

[0666] The antisense strand of survivin siRNA is: SEQ ID NO: 105: UGACAGAUAAGGAACCUGCTT. The 3'-terminal TT of both the sense and antisense strands of survivin siRNA are modified with dTdT.

[0667] Drug 30): a 2*mannose-A15 aptamer-survivin siRNA-DNA vector, wherein the DNA vector is group 22) of the aforementioned 26 backbone sequence nucleic acid vectors, the A15 aptamer is linked to the 5' end of the b sequence via the transition sequence TTTTT, two mannose groups are linked to the 5' end of the A15 aptamer and the 3' end of the b sequence, respectively, the sense strand of the survivin siRNA is linked to the 3' end of the c strand, and the antisense strand of the survivin siRNA is linked to the 3' end of the c strand via complementary pairing with the sense strand of the survivin siRNA;

[0668] Preferably, the sense strand of survivin siRNA is: SEQ ID NO: 104: UGCAGGUUCCUUAUCUGUCATT;

[0669] The antisense strand of survivin siRNA is: SEQ ID NO: 105: UGACAGAUAAGGAACCUGCdTT; the TT at the 3' end of both the antisense and sense strands of survivin siRNA is modified with dTdT;

[0670] Preferably, the sequence of the A15 aptamer is: SEQ ID NO: 129: CCCTCCTACATAGGG.

[0671] Drug 31): AS1411 aptamer-survivin siRNA-PSMA aptamer-3*AmiR-21-RNA vector, wherein the DNA vector is group 16) of the aforementioned 26 backbone sequence nucleic acid vectors, the PSMA aptamer is linked to the 3' end of sequence a via the transition sequence AA, the three AmiR-21s are tandemly linked to the 3' end of sequence b via the transition sequence AA, the sense strand of the survivin siRNA is linked to the 3' end of sequence c via the transition sequence AAA, the AS1411 aptamer and the antisense strand of the survivin siRNA are linked to the 3' end of sequence c via the transition sequence TT, and the AS1411 aptamer and the antisense strand of the survivin siRNA are linked to the 3' end of sequence c via complementary pairing of the antisense strand of the survivin siRNA with the sense strand of the survivin siRNA, wherein the first two nucleotides at the 5' end of sequence a, sequence b, and sequence c of the DNA vector are independently thiolated;

[0672] Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG;

[0673] Preferably, the sense strand of the survivin siRNA is: SEQ ID NO: 100: GCAGGUUCCUUAUCUGUCACAUU, and the antisense strand of the survivin siRNA is: SEQ ID NO: 300: UGUGACAGAUAAGGAACCUGCAG, and both the sense strand and the antisense strand of the survivin siRNA have thiolation modifications between the first 3 positions of the 5' end and the last 3 positions of the 3' end;

[0674] Preferably, the sequence of the PSMA aptamer is:

[0675] SEQ ID NO: 234: GGGACCGAAAAAGACCUGACUUCUAUACUAAGUCUACGUUCCC, the phosphate backbone between the last two nucleotides at the 3' end is thiolated;

[0676] Preferably, the sequence of AmiR-21 is: GAUAAGCU, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides.

[0677] Drug 32): 3*AmiR-21-ATP aptamer-FGF2 aptamer-DNA vector, wherein the DNA vector is group 15) of the aforementioned 26 backbone sequence nucleic acid vectors, three AmiR-21s are directly linked in tandem to the 5' end of sequence a, the ATP aptamer is linked to the 5' end of sequence b via the transition sequence TTTTT, and the FGF2 aptamer is linked to the 5' end of sequence c via U, wherein the first two nucleotides at the 3' end of sequence a, sequence b, and sequence c of the DNA vector independently have a thiolation modification;

[0678] Preferably, the sequence of the ATP aptamer is: SEQ ID NO: 135: ACCTGGGGAGTATTGGGGAGGAAGG, wherein the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0679] Preferably, the sequence of the FGF2 aptamer is:

[0680] SEQ ID NO: 183: GGGAUACUAGGGCAUUAAUGUUACCAGUGUAGUCCC, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0681] Preferably, the sequence of AmiR-21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides.

[0682] Drug 33): AS1411 aptamer-Survivin siRNA-PSMA aptamer-3*AmiR-21-DNA / RNA mixed vector, wherein the DNA-RNA mixed vector is group 18) of the aforementioned 26 backbone sequence nucleic acid vectors, the PSMA aptamer is linked to the 3' end of sequence a via the transition sequence AA, the three AmiR-21s are linked in tandem to the 3' end of sequence b via the transition sequence AA, the sense strand of the Survivin siRNA is linked to the 3' end of sequence c via the transition sequence AAAA, and the AS1411 aptamer is linked to the 5' end of the antisense strand of the Survivin siRNA via the transition sequence AA, the antisense strand of the Survivin siRNA is complementary to the sense strand of the Survivin siRNA, and the first two nucleotides at the 5' end of sequence b and sequence c of the DNA vector are independently thiolated;

[0683] Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, wherein the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0684] Preferably, the antisense strand of the Survivin siRNA is: SEQ ID NO: 300: UGUGACAGAUAAGGAACCUGCAG; the sense strand is: SEQ ID NO: 100: GCAGGUUCCUUAUCUGUCACAUU; both the sense and antisense strands of the Survivin siRNA have thiolation modifications on the phosphate backbone between the first three adjacent nucleotides at the 5' end and between the last three adjacent nucleotides at the 3' end;

[0685] Preferably, the sequence of the PSMA aptamer is:

[0686] SEQ ID NO: 234: GGGACCGAAAAAGACCUGACUUCUAUACUAAGUCUACGUUCCC, C and U have 2'-F modifications, A and G have 2'-OME modifications, and there is a thio modification on the phosphate backbone between the first two nucleotides at the 3' end;

[0687] Preferably, the sequence of AmiR-21 is: GAUAAGCU, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides.

[0688] Drug 34): 3*AmiR-21-AS1411 aptamer-FAP aptamer-DNA vector, wherein the RNA vector is the 15th group of nucleic acid vectors with the aforementioned 26 backbone sequences, the three AmiR-21s are connected in series to the 5' end of sequence a via the transition sequence TTTTTT, the AS1411 aptamer is connected to the 5' end of sequence b via the transition sequence TTTTT, and the FAP aptamer is connected to the 5' end of sequence c via the transition sequence TTTTT;

[0689] Preferably, the sequence of AmiR-21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides;

[0690] Preferably, the sequence of the AS1411 aptamer is:

[0691] SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0692] Preferably, the sequence of the FAP aptamer is:

[0693] SEQ ID NO: 188: CCGCTCGAGCTAGTCTGACAAAGAGAAACAC, the phosphate backbone between the first two nucleotides at the 5' end is thiolated.

[0694] Drug 35): AS1411 aptamer-Survivin siRNA-EpCAM aptamer-3*AmiR-21-DNA vector, wherein the DNA vector is the nucleic acid vector of group 14) among the aforementioned 26 backbone sequences, the AS1411 aptamer is linked to the 5' end of the survivin siRNA antisense strand via the transition sequence AA, the survivin siRNA sense strand is linked to the 3' end of the c sequence via the transition sequence AAAA, and the survivin siRNA antisense strand and the survivin siRNA sense strand are complementary and linked; three AmiR-21s are linked in tandem to the 3' end of the b sequence via the transition sequence AA, and the EpCAM aptamer is linked to the 3' end of the a sequence via the transition sequence AA, wherein the first two nucleotides at the 5' end of the b sequence of the DNA vector are independently thiolated;

[0695] Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, wherein the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0696] Preferably, the survivin siRNA antisense strand is: SEQ ID NO: 300: UGUGACAGAUAAGGAACCUGCAG, and the survivin siRNA sense strand is: SEQ ID NO: 100: GCAGGUUCCUUAUCUGUCACAUU, and both the sense and antisense strands of the survivin siRNA have thiolation modifications between the first three adjacent positions at the 5' end and between the last three adjacent positions at the 3' end. The 5' end of the survivin siRNA antisense strand has 2'-F modifications at positions 2, 6, 8, 9, 12, 14, and 16, and the rest are 2'-OMe modified. The 7, 9, 10, and 11 positions of the survivin siRNA sense strand are 2'-F modifications, and the rest are 2'-OMe modified.

[0697] Preferably, the sequence of AmiR-21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides;

[0698] Preferably, the sequence of the EpCAM aptamer is: SEQ ID NO: 179: GCGACUGGUUACCCGGUCG, C and U have 2'-F modification, A and G have 2'-OME modification;

[0699] There is a thiolation modification in the phosphate backbone between the first three nucleotides at the 5' end and the last three nucleotides at the 3' end.

[0700] Drug 36): IL-4RA aptamer-TGF-β aptamer-PD-L1 aptamer-2*AmiR-21-DNA vector, wherein the DNA vector is group 15) of the aforementioned 26 backbone sequence nucleic acid vectors, the IL-4RA aptamer is linked to the 5' end of sequence a via an AmiR-21, the TGF-β aptamer is linked to the 5' end of sequence b via the transition sequence TTTTT, and the PD-L1 aptamer is linked to the 5' end of sequence c via an AmiR-21, wherein the first two nucleotides at the 3' end of sequence a, sequence b, and sequence c of the DNA vector independently have a thiolation modification;

[0701] Preferably, the sequence of the IL-4RA aptamer is:

[0702] SEQ ID NO: 203: AAAAAGCAACAGGGUGCUCCAUGCGCAUGGAACCUGCGCG, the phosphate backbone between the first four adjacent nucleotides at the 5' end is thiolated;

[0703] Preferably, the sequence of the TGF-β aptamer is:

[0704] SEQ ID NO: 269: ACATTGCTGCGTGATCGCCTCACATGGGTTTGTCTGGTCGATTTGGAGGTGGTGGGTGGC, the phosphate backbone between the first four adjacent nucleotides at the 5' end is thiolated;

[0705] Preferably, the sequence of the PD-L1 aptamer is:

[0706] SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, the phosphate backbone between the first four adjacent nucleotides at the 5' end is thiolated;

[0707] Preferably, the sequence of AmiR-21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides.

[0708] Drug 37): AS1411 aptamer-ATAD2 siRNA-GPC3 aptamer-5*AimR-21-DNA vector, wherein the DNA vector is group 19) of the aforementioned 26 types of nucleic acid vectors with backbone sequences, the AS1411 aptamer is linked to the 5' end of the antisense strand of the ATAD2 siRNA via one AimR-21, the sense strand of the ATAD2 siRNA is linked to the 3' end of the c sequence via one AimR-21, the antisense strand of the ATAD2 siRNA and the sense strand of the ATAD2 siRNA are complementary and linked, one AimR-21 is linked to the 3' end of the a sequence, the GPC3 aptamer is linked to the 5' end of the b sequence via one AimR-21, and one AimR-21 is linked to the 5' end of the c sequence, wherein the first two nucleotides at the 5' end of the b sequence of the DNA vector are independently thiolated;

[0709] Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, wherein the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0710] Preferably, the antisense strand of the ATAD2 siRNA is: SEQ ID NO: 68: GCGUCGAAGUUGUAGGAUUUU, and the sense strand is: SEQ ID NO: 69: AAUCCUACAACUUCGACGCUU. Both the sense and antisense strands of the ATAD2 siRNA have thiolation modifications between the first three adjacent positions at the 5' end and the last three adjacent positions at the 3' end. Positions 2, 6, 8, 9, 12, 14, and 16 from the 5' end have 2'-F modifications, and the rest have 2'-OME modifications.

[0711] The sequence of the GPC3 aptamer is: SEQ ID NO: 190: TAACGCTGACCTTAGCTGCATGGCTTTACATGTTCCA, with a thiolation modification of the phosphate backbone between the first three adjacent nucleotides at the 5' end;

[0712] Preferably, the sequence of AmiR-21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides.

[0713] Drug 38): Vap7 aptamer-TGF-β aptamer-Act-12c aptamer-3*AmiR-21-DNA vector, wherein the DNA vector is group 15) of the aforementioned 26 backbone sequence nucleic acid vectors, the Vap7 aptamer is linked to the 5' end of sequence a via two tandem AmiR-21s, the TGF-β aptamer is linked to the 5' end of sequence b via the transition sequence TTTTT, and the Act-12c aptamer is linked to the 5' end of sequence c via one AmiR-21, wherein the first two nucleotides at the 3' end of sequence a, sequence b, and sequence c of the DNA vector independently have a thiolation modification;

[0714] Preferably, the sequence of the Vap7 aptamer is: SEQ ID NO: 277: TGGTGGGGGTGGACGGGCCGGGTAGA, wherein the phosphate backbone between the first four adjacent nucleotides at the 5' end is thiolated;

[0715] Preferably, the sequence of AmiR-21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides;

[0716] Preferably, the sequence of the TGF-β aptamer is:

[0717] SEQ ID NO: 269: ACATTGCTGCGTGATCGCCTCACATGGGTTTGTCTGGTCGATTTGGAGGTGGTGGGTGGC, a thiolation modification exists at the phosphate backbone between the first four adjacent nucleotides at the 5' end;

[0718] Preferably, the sequence of the Act-12c aptamer is:

[0719] SEQ ID NO: 137: CGGGGAAAGTCACGGGGGGTTTCAGATGTTCTGATCGGTGTGGAG, a thiolation modification exists in the phosphate backbone between the first four adjacent nucleotides at the 5' end.

[0720] Drug 39): AS1411 aptamer-3*AmiR-21-IL-4RA aptamer-VCAM-1 aptamer-DNA vector, wherein the DNA vector is group 15) of the aforementioned 26 backbone sequence nucleic acid vectors, the AS1411 aptamer is sequentially linked to the 5' end of sequence a via a transition sequence TTTTT and three tandem AmiRs, the IL-4RA aptamer and VCAM-1 aptamer are linked to the 5' end of sequence b and the 5' end of sequence c, respectively, via a transition sequence TTTTT, wherein the first two nucleotides at the 3' end of sequences a, b, and c of the DNA vector are independently thiolated;

[0721] Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: G*GTGGTGGTGGTTGTGGTGGTGGTGG, wherein there is a thiolation modification on the phosphate backbone between the first two nucleotides at the 5' end;

[0722] Preferably, the sequence of AmiR-21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides;

[0723] Preferably, the sequence of the IL-4RA aptamer is:

[0724] SEQ ID NO: 203: AAAAAGCAACAGGGUGCUCCAUGCGCAUGGAACCUGCGCG, a thio modification is present at the phosphate backbone between the first two nucleotides at the 5' end, C or U has a 2'-F modification, and A or G has a 2'-OME modification;

[0725] Preferably, the sequence of the VCAM-1 aptamer is:

[0726] SEQ ID NO: 284: GGACACGGCAAAGGGGTATAGCCTACCGGACCGTGAACATGGAATGGTGTGCTGCGTGG, a thiolation modification exists in the phosphate backbone between the first two nucleotides at the 5' end.

[0727] Drug 40): GPC1 aptamer-AS1411 aptamer-EpCAM aptamer-2*AmiR-21-DNA vector, wherein the DNA vector is group 14) of the aforementioned 26 backbone sequence nucleic acid vectors, the GPC1 aptamer is linked to the 5' end of sequence a via an AmiR-21, the AS1411 aptamer is linked to the 5' end of sequence b via a transition sequence TTTTT, and the EpCAM aptamer is linked to the 5' end of sequence c via an AmiR-21, wherein the first three nucleotides at the 3' end of sequence a, sequence b, and sequence c of the DNA vector are each independently thiolated, and the first two nucleotides at the 3' end are each independently 2'-O-MOE modified;

[0728] Preferably, the sequence of the GPC1 aptamer is: SEQ ID NO: 189: AACGGAGTGTGGCTAACTCGA, wherein there is a thiolation modification in the phosphate backbone between the first four adjacent nucleotides at the 5' end;

[0729] Preferably, the sequence of AmiR-21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides;

[0730] Preferably, the sequence of the AS1411 aptamer is:

[0731] SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, thiolation modification at the phosphate backbone between nucleotides 1-2, 3-4, 13-14, 16-17, and 24-25 from the 5' end;

[0732] Preferably, the sequence of the EpCAM aptamer is: SEQ ID NO: 179: GCGACUGGUUACCCGGUCG, wherein the phosphate backbone between the first four adjacent nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification.

[0733] Drug 41): 3*AmiR-21-AS1411 aptamer-CD40 aptamer-2*biotin-DNA vector, wherein the DNA vector is group 1) of the aforementioned 26 backbone sequence nucleic acid vectors, three AmiR-21s are respectively linked to the 5' end, 3' end, and 3' end of sequence a, and the 3' end of sequence b, the AS1411 aptamer is linked to the 5' end of sequence b via the transition sequence TTTTT, the CD40 aptamer is linked to the 5' end of sequence c via the transition sequence TTTTT, one biotin is modified at the 3' end of the AmiR-21 located at the 3' end of sequence a, and another biotin is modified at the 3' end of sequence c;

[0734] Preferably, the sequence of AmiR-21 is: GATAAGCT, with each nucleotide having a locked nucleic acid modification;

[0735] Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG;

[0736] Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG.

[0737] Drug 42): IL-4RA aptamer-VCAM-12D aptamer-PD-L1 aptamer-3*AmiR-21-DNA vector, wherein the DNA vector is group 3) of the aforementioned 26 backbone sequence nucleic acid vectors, the IL-4RA aptamer is linked to the 5' end of sequence a via the first AmiR21, the VCAM-12d aptamer is linked to the 5' end of sequence b via the second AmiR21, and the PD-L1 aptamer is linked to the 5' end of sequence c via the third AmiR21, wherein the first two nucleotides at the 3' end of sequence a, sequence b, and sequence c of the DNA vector independently have a thiolation modification;

[0738] Preferably, the sequence of the IL-4RA aptamer is:

[0739] SEQ ID NO: 203: AAAAAGCAACAGGGUGCUCCAUGCGCAUGGAACCUGCGCG, wherein the phosphate backbone between the first four adjacent nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification;

[0740] Preferably, the sequence of the VCAM-12d aptamer is:

[0741] SEQ ID NO: 285: AGGGAATCTTGCCTAGGGAGGGAGTAGCGAAAGGGCTCA, a thiolation modification exists at the phosphate backbone between the first four adjacent nucleotides at the 5' end;

[0742] Preferably, the sequence of the PD-L1 aptamer is:

[0743] SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, a thiolation modification exists at the phosphate backbone between the first four adjacent nucleotides at the 5' end;

[0744] Preferably, the sequence of AmiR-21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides.

[0745] Drug 43): TAPsiRNA-3*AmiR-21-2*AS1411 aptamer-DNA vector, wherein the DNA vector is group 6) of the aforementioned 26 backbone sequence nucleic acid vectors, the sense strand of the TAPsiRNA is linked to the 3' end of the c sequence via the transition sequence AAAA, an AS1411 aptamer is linked to the antisense strand of the TAPsiRNA via the transition sequence AAAA, and the AS1411 aptamer is linked to the 3' end of the c sequence via complementary pairing of the antisense and sense strands, another AS1411 aptamer is linked to the 3' end of the a sequence via the transition sequence AAAA, and three AmiR-21s are tandemly linked to the 3' end of the b sequence via the transition sequence AA, and the first two nucleotides at the 5' end of the a sequence, b sequence, and c sequence of the DNA vector are independently thiolated;

[0746] Preferably, the sense strand sequence of TAPsiRNA is: SEQ ID NO: 301: GCUGCACACGGUUCAGAAU, and the antisense strand sequence is: SEQ ID NO: 109: AUUCUGAACCGUGUGCAGCUU. Both the sense and antisense strands of TAPsiRNA have thiolation modifications between the first three bases at the 5' end and the last three bases at the 3' end. Positions 2, 6, 8, 9, 12, 14, and 16 at the 5' end of the antisense strand of TAPsiRNA are 2'-F modifications, and the rest are 2'-OME modifications. Positions 7, 9, 10, and 11 at the 5' end of the sense strand of TAPsiRNA are 2'-F modifications, and the rest are 2'-OME modifications.

[0747] Preferably, the sequence of AmiR-21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides;

[0748] Preferably, the sequence of AS1411-1 is:

[0749] SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated.

[0750] Drug 44): PD-1 aptamer-AS1411 aptamer-PD-L1 aptamer-3*AmiR-21-DNA vector, wherein the DNA vector is group 3) of the aforementioned 26 backbone sequence nucleic acid vectors, the PD-1 aptamer is linked to the 5' end of sequence a via one AmiR-21, the AS1411 aptamer is linked to the 5' end of sequence b via one AmiR-21, and the PD-L1 aptamer is linked to the 5' end of sequence c via one AmiR-21, and the first two nucleotides at the 3' end of sequence a, sequence b, and sequence c of the DNA vector are independently thiolated;

[0751] Preferably, the sequence of the PD-1 aptamer is: SEQ ID NO: 253: AGCGGTGACGGCACAGACGGTACAGTTCCCGTCCCTGCACTACACGTATGCCGCT, wherein the phosphate backbone between the first four adjacent nucleotides at the 5' end is thiolated;

[0752] Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, wherein the phosphate backbone between the first two adjacent nucleotides at the 5' end is thiolated;

[0753] Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, wherein the phosphate backbone between the first four adjacent nucleotides at the 5' end is thiolated;

[0754] Preferably, the sequence of AmiR-21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides.

[0755] Drug 45): CpG1826-CD40 aptamer-AmiR-21-3*biotin-DNA vector, wherein the DNA vector is the nucleic acid vector of group 13) among the aforementioned 26 backbone sequences, CpG1826 is linked to the 5' end of sequence a via a transition sequence, the CD40 aptamer is linked to the 5' end of sequence b via a transition sequence, and AmiR-21 is linked to the 5' end of sequence c via a transition sequence, and three biotins are linked to the 3' ends of sequence a, sequence b, and sequence c, respectively;

[0756] Preferably, the sequence of CpG1826 is: SEQ ID NO: 59: TCCATGACGTTCCTGACG, wherein the phosphate backbone between two adjacent nucleotides is thiolated;

[0757] Preferably, the transition sequence is TTTTT;

[0758] Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG;

[0759] Preferably, the sequence of AmiR21 is GATAAGCT, with each nucleotide having a locked nucleic acid modification.

[0760] Drug 46): ATP aptamer-AmiR-21-FGF2 aptamer-AmiR-1306-DNA vector, wherein, in the DNA vector, the a sequence is: SEQ ID NO: 18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC; the b sequence is: SEQ ID NO: 19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG; the c sequence is: SEQ ID NO: 31: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGC; the ATP aptamer is connected to the 5' end of the a sequence via a transition sequence TTTTT, the FGF2 aptamer is connected to the 5' end of the b sequence via a transition sequence U, and AmiR1306 and AmiR-21 are connected to the 5' end of the c sequence in sequence.

[0761] The sequence of the ATP aptamer is SEQ ID NO: 136: GGGAGGACGATGCGGAGGAAGGGTAGG, with a thioate modification on the phosphate backbone between the first four nucleotides at the 5' end;

[0762] The sequence of the FGF2 aptamer is SEQ ID NO: 183: GGGAUACUAGGGCAUUAAUGUUACCAGUGUAGUCCC, wherein C and U have 2'-F modifications;

[0763] The sequence of AmiR1306 is: SEQ ID NO: 127: CATCACCACCAGAGCCAACGTC, wherein the phosphate backbone between the first five nucleotides at the 5' end has a thioate modification;

[0764] The sequence of AmiR-21 is: GATAAGCT, and each nucleotide is modified with a locked nucleic acid.

[0765] Drug 47): CD16a aptamer-CTLA-4 aptamer-PD-L1 aptamer-DNA vector, wherein the DNA vector is the nucleic acid vector of group 9) among the aforementioned 26 backbone sequences, the CD16a aptamer is connected to the 5' end of sequence a via a transition sequence, the CTLA-4 aptamer is connected to the 5' end of sequence b via a transition sequence, and the PD-L1 aptamer is connected to the 5' end of sequence c, and the first two nucleotides at the 3' end of sequence a, sequence b, and sequence c of the DNA vector are independently thiolated;

[0766] Preferably, the sequence of the CD16a aptamer is:

[0767] SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0768] Preferably, the sequence of the CTLA-4 aptamer is:

[0769] SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU, the phosphate backbone between the first two nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification;

[0770] Preferably, the sequence of the PD-L1 aptamer is:

[0771] SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, the phosphate backbone between the first two nucleotides at the 5' end is thiolated.

[0772] Drug 48): CD16a aptamer-Act-12c aptamer-PD-L1 aptamer-DNA vector, wherein the DNA vector is the nucleic acid vector of group 9) among the aforementioned 26 backbone sequences, the CD16a aptamer is connected to the 5' end of sequence a via a transition sequence, the Act-12c aptamer is connected to the 5' end of sequence b via a transition sequence, and the PD-L1 aptamer is connected to the 5' end of sequence c, and the first two nucleotides at the 3' end of sequence a, sequence b, and sequence c of the DNA vector are independently thiolated;

[0773] Preferably, the sequence of the CD16a aptamer is:

[0774] SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0775] Preferably, the sequence of the Act-12c aptamer is:

[0776] SEQ ID NO: 137: CGGGGAAAGTCACGGGGGGTTTCAGATGTTCTGATCGGTGTGGAG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0777] Preferably, the sequence of the PD-L1 aptamer is:

[0778] SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, the phosphate backbone between the first two nucleotides at the 5' end is thiolated.

[0779] Drug 49): CTLA-4 aptamer-PD-L1 aptamer-PD1 aptamer-DNA vector, wherein the DNA vector is the 5th group of nucleic acid vectors of the aforementioned 26 backbone sequences,

[0780] The PD-L1 aptamer is sequentially connected to the transition sequence and the complementary sequence A' of the single-stranded bridge sequence A. The single-stranded bridge sequence A is located at the 3' end of the a sequence. The PD-L1 aptamer is connected to the 3' end of the a sequence through the complementary pairing of the complementary sequence A' and the single-stranded bridge sequence A.

[0781] The PD1 aptamer is sequentially connected to the transition sequence and the complementary sequence B' of the single-stranded bridge sequence B. The single-stranded bridge sequence B is located at the 3' end of the b sequence. The PD-L1 aptamer is connected to the 3' end of the b sequence through the complementary pairing of the complementary sequence B' and the single-stranded bridge sequence B.

[0782] The CTLA-4 aptamer is connected to the complementary sequence C' of the single-chain bridge sequence C. The single-chain bridge sequence C is located at the 3' end of the C sequence. The PD-L1 aptamer is connected to the 3' end of the C sequence through the complementary pairing of the complementary sequence C' and the single-chain bridge sequence C.

[0783] Preferably, the sequence of the PD-L1 aptamer is:

[0784] SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, the phosphate backbone between the first three adjacent nucleotides at the 5' end is thiolated;

[0785] Preferably, the sequence of the PD1 aptamer is:

[0786] SEQ ID NO: 254: ACCGACAGTGAAGGACTCAGCGAACTCTCAGACTCGGTTC, the phosphate backbone between the first three adjacent nucleotides at the 5' end is thiolated;

[0787] Preferably, the sequence of the CTLA-4 aptamer is:

[0788] SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU, the phosphate backbone between the first three nucleotides at the 5' end has a thio modification, the ribose sugars of the first two nucleotides at the 5' end have a 2'-O-MOE modification, and the remaining C or U have a 2'-F modification;

[0789] Preferably, the single-stranded connecting bridge sequence A is: SEQ ID NO: 7: TGTAGCACGGTGGC, and the complementary sequence A' is SEQ ID NO: 8: GCCACCGTGCTACA;

[0790] Preferably, the single-stranded connecting bridge sequence B is: SEQ ID NO: 7: TGTAGCACGGTGGC, and the complementary sequence B' is SEQ ID NO: 8: GCCACCGTGCTACA;

[0791] Preferably, the single-stranded connecting bridge sequence C is: SEQ ID NO: 11: TGCTGCTGCTGCTG, and the complementary sequence C' is SEQ ID NO: 12: CAGCAGCAGCAGCA.

[0792] Drug 50): PD1 aptamer-IL-4Ra aptamer-OX40 aptamer-DNA vector, wherein the DNA vector is group 6) of the aforementioned 26 backbone sequence nucleic acid vectors, the PD1 aptamer is linked to the 5' end of sequence a via a transition sequence AAA, the IL-4Ra aptamer is linked to the 5' end of sequence b via a transition sequence AAA, and the OX40 aptamer is linked to the 5' end of sequence c via a transition sequence AAA, and the first three nucleotides at the 3' end of sequences a, b, and c of the DNA vector are independently thiolated;

[0793] Preferably, the sequence of the PD1 aptamer is:

[0794] SEQ ID NO: 253: AGCGGTGACGGCACAGACGGTACAGTTCCCGTCCCTGCACTACACGTATGCCGCT, the phosphate backbone between the first four adjacent nucleotides at the 5' end is thiolated;

[0795] Preferably, the sequence of the IL-4Ra aptamer is:

[0796] SEQ ID NO: 203: AAAAAGCAACAGGGUGCUCCAUGCGCAUGGAACCUGCGCG, the phosphate backbone between the first four adjacent nucleotides at the 5' end is thiolated;

[0797] Preferably, the sequence of the OX40 aptamer is:

[0798] SEQ ID NO: 229: CAGUCUGCAUCGUAGGAAUCGCCACCGUAUACUUUCCCAC, the phosphate backbone between the first 4 adjacent nucleotides at the 5' end has a thio modification, and the ribose of the first 3 nucleotides at the 5' end has a 2'-O-MOE modification, the remaining C or U has a 2'-F modification, and the A or G has a 2'-OME modification.

[0799] Drug 51): CD16a aptamer-OX40 aptamer-PD-L1 aptamer-DNA vector, wherein the DNA vector is group 3) of the aforementioned 26 backbone sequence nucleic acid vectors, the CD16a aptamer is connected to the 5' end of sequence a via a transition sequence, the OX40 aptamer is connected to the 5' end of sequence b via a transition sequence, and the PD-L1 aptamer is connected to the 5' end of sequence c via a transition sequence, and the first two nucleotides at the 3' end of sequence a, sequence b, and sequence c of the DNA vector are independently thiolated;

[0800] Preferably, the sequence of the CD16a aptamer is:

[0801] SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0802] Preferably, the sequence of the OX40 aptamer is:

[0803] SEQ ID NO: 230: GGGAUGCGGAAAAAAGAACACUUCCGAUUAGGGCCCACCCUAACGGCCGCAGAC, C or U has a 2'-F modification, A or G has a 2'-OME modification, and the phosphate backbone between the first two nucleotides at the 5' end has a thio modification;

[0804] Preferably, the sequence of the PD-L1 aptamer is:

[0805] SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, the phosphate backbone between the first two nucleotides at the 5' end is thiolated.

[0806] Drug 52): CD16a aptamer-VEGF165 aptamer-PD-L1 aptamer-DNA vector, wherein the DNA vector is group 3) of the aforementioned 26 backbone sequence nucleic acid vectors, the CD16a aptamer is connected to the 5' end of sequence a via a transition sequence, the VEGF165 aptamer is connected to the 5' end of sequence b via a transition sequence, and the PD-L1 aptamer is connected to the 5' end of sequence c via a transition sequence, and the first two nucleotides at the 3' end of sequence a, sequence b, and sequence c of the DNA vector are independently thiolated;

[0807] Preferably, the sequence of the CD16a aptamer is:

[0808] SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0809] Preferably, the sequence of the VEGF165 aptamer is:

[0810] SEQ ID NO: 280: CGGAAUCAGUGAAUGCUUAUACAUCCG, C or U has a 2'-F modification, A or G has a 2'-OME modification, and the phosphate backbone between the first two nucleotides at the 5' end has a thio modification;

[0811] Preferably, the sequence of the PD-L1 aptamer is:

[0812] SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, the phosphate backbone between the first two nucleotides at the 5' end is thiolated.

[0813] Drug 53): CD16a aptamer-CTLA4 aptamer-TIM3 aptamer-DNA vector, wherein the DNA vector is group 3) of the aforementioned 26 backbone sequence nucleic acid vectors, the CD16a aptamer is linked to the 5' end of sequence a via a transition sequence, the CTLA4 aptamer is linked to the 5' end of sequence b via a transition sequence, and the TIM3 aptamer is linked to the 5' end of sequence c via a transition sequence, and the first two nucleotides at the 3' end of sequences a, b, and c of the DNA vector are independently thiolated;

[0814] Preferably, the sequence of the CD16a aptamer is:

[0815] SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0816] Preferably, the sequence of the CTLA4 aptamer is:

[0817] SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU, the phosphate backbone between the first two nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification;

[0818] Preferably, the sequence of the TIM3 aptamer is:

[0819] SEQ ID NO: 270: GGGAGAGGACCAGUAGCCACUAUGGUGUUGGAGCUAGCGGCAGAGCGUCGCGGUCCC UCCC, the phosphate backbone between the first two nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification.

[0820] Drug 54): PD-1 aptamer-CTLA-4 aptamer-LAG-3 aptamer-DNA vector, wherein the DNA vector is group 3) of the aforementioned 26 backbone sequence nucleic acid vectors, the PD-L1 aptamer is linked to the 5' end of sequence a via a transition sequence, the CTLA-4 aptamer is linked to the 5' end of sequence b via a transition sequence, and the LAG-3 aptamer is linked to the 5' end of sequence c via a transition sequence, and the first two nucleotides at the 3' end of sequence a, sequence b, and sequence c of the DNA vector are independently thiolated;

[0821] Preferably, the sequence of the PD-1 aptamer is:

[0822] SEQ ID NO: 253: AGCGGTGACGGCACAGACGGTACAGTTCCCGTCCCTGCACTACACGTATGCCGCT, the phosphate backbone between the first two nucleotides at the 5' end has a thiolation modification;

[0823] Preferably, the sequence of the CTLA-4 aptamer is:

[0824] SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU, the phosphate backbone between the first two nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification;

[0825] Preferably, the sequence of the LAG-3 aptamer is:

[0826] SEQ ID NO: 206: GGGAGAGAGAUAUAAGGGCCUCCUGAUACCCGCUGCUAUCUGGACCGAUCCCAUUACCAAAUUCUCUCCC, the phosphate backbone between the first two nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification.

[0827] Drug 55): CD16a aptamer-Act-12c aptamer-MUC1 aptamer-DNA vector, wherein the DNA vector is the nucleic acid vector of group 3) among the aforementioned 26 backbone sequences, the CD16a aptamer is linked to the 5' end of sequence a via a transition sequence, the Act-12c aptamer is linked to the 5' end of sequence b via a transition sequence, and the MUC1 aptamer is linked to the 5' end of sequence c via a transition sequence, and the first two nucleotides at the 3' end of sequence a, sequence b, and sequence c of the DNA vector are independently thiolated;

[0828] Preferably, the sequence of the CD16a aptamer is:

[0829] SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0830] Preferably, the sequence of the Act-12c aptamer is:

[0831] SEQ ID NO: 137: CGGGGAAAGTCACGGGGGGTTTCAGATGTTCTGATCGGTGTGGAG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0832] Preferably, the sequence of the MUC1 aptamer is: SEQ ID NO: 209: GAAGTGAAAATGACAGAACACAACA.

[0833] Drug 56): CD16a aptamer-TGF-β aptamer-PD-L1 aptamer-DNA vector, wherein the DNA vector is the nucleic acid vector of group 3) among the aforementioned 26 backbone sequences, the CD16a aptamer is connected to the 5' end of sequence a via a transition sequence, the TGF-β aptamer is connected to the 5' end of sequence b via a transition sequence, and the PD-L1 aptamer is connected to the 5' end of sequence a via a transition sequence, and the first two nucleotides at the 3' end of sequence a, sequence b, and sequence c of the DNA vector are independently thiolated;

[0834] Preferably, the sequence of the CD16a aptamer is:

[0835] SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0836] Preferably, the sequence of the TGF-β aptamer is:

[0837] SEQ ID NO: 269: ACATTGCTGCGTGATCGCCTCACATGGGTTTGTCTGGTCGATTTGGAGGTGGTGGGTGGC, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0838] Preferably, the sequence of the PD-L1 aptamer is:

[0839] SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, the phosphate backbone between the first two nucleotides at the 5' end is thiolated.

[0840] Drug 57): CD16a aptamer-CD40 aptamer-CTLA-4 aptamer-DNA vector, wherein the DNA vector is the nucleic acid vector of group 3) among the aforementioned 26 backbone sequences, the CD16a aptamer is linked to the 5' end of sequence a via a transition sequence, the CD40 aptamer is linked to the 5' end of sequence b via a transition sequence, and the CTLA-4 aptamer is linked to the 5' end of sequence c via a transition sequence, and the first two nucleotides at the 3' end of sequence a, sequence b, and sequence c of the DNA vector are independently thiolated;

[0841] Preferably, the sequence of the CD16a aptamer is:

[0842] SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0843] Preferably, the sequence of the CD40 aptamer is:

[0844] SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0845] Preferably, the sequence of the CTLA-4 aptamer is:

[0846] SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU, the phosphate backbone between the first two nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification.

[0847] Drug 58): HER2 aptamer-HER3 aptamer-CD40 aptamer-CD16a aptamer-DNA vector, wherein the DNA vector is group 7) of the aforementioned 26 backbone sequence nucleic acid vectors, the HER3 aptamer is linked to the 5' end of sequence a via a transition sequence AA, the HER2 aptamer is linked to the 5' end of sequence c via a transition sequence AA, the CD40 aptamer and the CD16a aptamer are linked to the 5' and 3' ends of sequence b, respectively, via transition sequences AA, and the first two nucleotides at the 3' ends of sequence a and sequence c of the DNA vector are independently thiolated;

[0848] Preferably, the sequence of the HER2 aptamer is:

[0849] SEQ ID NO: 194: AGCCGCGAGGGGAGGGAUAGGGUAGGGCGCGGCU, the phosphate backbone between the first two nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification;

[0850] Preferably, the sequence of the HER3 aptamer is:

[0851] SEQ ID NO: 197: CAGCGAAAGUUGCGUAUGGGUCACAUCGCAGGCACAUGUCAUCUGGGCG, the phosphate backbone between the first two nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification;

[0852] Preferably, the sequence of the CD40 aptamer is:

[0853] SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0854] Preferably, the sequence of the CD16a aptamer is:

[0855] SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated.

[0856] Drug 59): CD16a aptamer-Act-12c aptamer-CTLA-4 aptamer-GPC1 aptamer-DNA vector, wherein the DNA vector is group 10) of the aforementioned 26 backbone sequence nucleic acid vectors, the CD16a aptamer is linked to the 5' end of sequence a via a transition sequence TTTTT, the Act-12c aptamer is linked to the 5' end of sequence b via a transition sequence TTTTT, the CTLA-4 aptamer and the GPC1 aptamer are linked to the 5' and 3' ends of sequence c, respectively, via a transition sequence TTT, and the first two nucleotides at the 3' end of sequence a and sequence b of the DNA vector are independently thiolated;

[0857] Preferably, the sequence of the CD16a aptamer is:

[0858] SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0859] Preferably, the sequence of the Act-12c aptamer is:

[0860] SEQ ID NO: 137: CGGGGAAAGTCACGGGGGGTTTCAGATGTTCTGATCGGTGTGGAG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0861] Preferably, the sequence of the CTLA-4 aptamer is:

[0862] SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU, the phosphate backbone between the first two nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification;

[0863] Preferably, the sequence of the GPC1 aptamer is:

[0864] SEQ ID NO: 189: AACGGAGTGTGGCTAACTCGA, the phosphate backbone between the last two nucleotides at the 3' end is thiolated.

[0865] Drug 60): CD16a aptamer-HER3 aptamer-VEGF165 aptamer-DNA vector, wherein the DNA vector is group 3) of the aforementioned 26 backbone sequence nucleic acid vectors, the CD16a aptamer is linked to the 5' end of sequence a via the transition sequence TTTTT, the HER3 aptamer is linked to the 5' end of sequence b via the transition sequence TTTTT, and the VEGF165 aptamer is linked to the 5' end of sequence c via the transition sequence TTTTT, and the first two nucleotides at the 3' end of sequence a, sequence b, and sequence c of the DNA vector are independently thiolated;

[0866] Preferably, the sequence of the CD16a aptamer is:

[0867] SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0868] Preferably, the sequence of the HER3 aptamer is:

[0869] SEQ ID NO: 197: CAGCGAAAGUUGCGUAUGGGUCACAUCGCAGGCACAUGUCAUCUGGGCG, the phosphate backbone between the first two nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification;

[0870] Preferably, the sequence of the VEGF165 aptamer is:

[0871] SEQ ID NO: 280: CGGAAUCAGUGAAUGCUUAUACAUCCG, the phosphate backbone between the first two nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification.

[0872] Drug 61): VEGF aptamer-GPC1 aptamer-PD-L1 aptamer-CD16a aptamer-DNA vector, wherein the DNA vector is group 11) of the aforementioned 26 backbone sequence nucleic acid vectors, the VEGF aptamer and GPC1 aptamer are linked to the 5' and 3' ends of sequence a, respectively, via the transition sequence TTTTT, the PD-L1 aptamer and CD16a aptamer are linked to the 5' and 5' ends of sequence b, respectively, via the transition sequence TTTTT, and the first two nucleotides at the 3' ends of sequence b and sequence c of the DNA vector are independently thiolated;

[0873] Preferably, the sequence of the VEGF aptamer is:

[0874] SEQ ID NO: 279: GGTGGGGGTGGACGGGCCGGGTAGA, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0875] Preferably, the sequence of the GPC1 aptamer is:

[0876] SEQ ID NO: 189: AACGGAGTGTGGCTAACTCG*A, the phosphate backbone between the last two nucleotides at the 3' end is thiolated;

[0877] Preferably, the sequence of the PD-L1 aptamer is:

[0878] SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0879] Preferably, the sequence of the CD16a aptamer is:

[0880] SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated.

[0881] Drug 62): PD-1 aptamer-PD-L1 aptamer-2*AmiR21-Act-12c aptamer-DNA vector, wherein the DNA vector is group 3) of the aforementioned 26 backbone sequence nucleic acid vectors, the PD-1 aptamer is linked to the 5' end of sequence a via one AmiR21, the PD-L1 aptamer is linked to the 5' end of sequence b via another AmiR21, and the Act-12c aptamer is linked to the 5' end of sequence c via the transition sequence TTTTT, and the first two nucleotides at the 3' end of sequence a, sequence b, and sequence c of the DNA vector are independently thiolated;

[0882] Preferably, the sequence of the PD-1 aptamer is:

[0883] SEQ ID NO: 253: AGCGGTGACGGCACAGACGGTACAGTTCCCGTCCCTGCACTACACGTATGCCGCT, the phosphate backbone between the first four adjacent nucleotides at the 5' end is thiolated;

[0884] Preferably, the sequence of the PD-L1 aptamer is:

[0885] SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, the phosphate backbone between the first four adjacent nucleotides at the 5' end is thiolated;

[0886] Preferably, the sequence of the Act-12c aptamer is:

[0887] SEQ ID NO: 137: CGGGGAAAGTCACGGGGGGTTTCAGATGTTCTGATCGGTGTGGAG, the phosphate backbone between the first four adjacent nucleotides at the 5' end is thiolated;

[0888] Preferably, the sequence of AmiR21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides.

[0889] Drug 63): Her3 aptamer-EGFR siRNA-AS1411 aptamer-Survivin siRNA-Her2 aptamer-DNA vector, wherein the DNA vector is the nucleic acid vector of group 14) among the aforementioned 26 backbone sequences, the AS1411 aptamer is linked to the 3' end of sequence a via the transition sequence AAAA, the Her2 aptamer is linked to the 3' end of sequence b via the transition sequence AAAA, the positive strand of the EGFR siRNA is linked to the 3' end of sequence c via the transition sequence AAAA; the positive strand of the Survivin siRNA is linked to the 3' end of sequence b via the transition sequence AAAA, and the first two nucleotides at the 5' end of sequence a, sequence b, and sequence c of the DNA vector are independently thiolated.

[0890] The Her3 aptamer was linked to the antisense strand of the EGFR siRNA via the transition sequence AA and was attached to the 3′ end of the c sequence through complementary pairing of the antisense strand of the EGFR siRNA with the sense strand of the EGFR siRNA;

[0891] The Her2 aptamer is linked to the antisense strand of Survivin siRNA through the transition sequence AA and is linked to the 3' end of the b sequence through complementary pairing between the antisense strand of Survivin siRNA and the sense strand of Survivin siRNA;

[0892] Preferably, the sequence of the Her3 aptamer is:

[0893] SEQ ID NO: 197: CAGCGAAAGUUGCGUAUGGGUCACAUCGCAGGCACAUGUCAUCUGGGCG, the phosphate backbone between the first three adjacent nucleotides at the 5' end is thiolated,

[0894] Preferably, the antisense strand of the EGFR siRNA is: SEQ ID NO: 302: AAUUAGAUAAGACUGCUAAGGCA, and the sense strand is: SEQ ID NO: 82: CCUUAGCAGUCUUAUCUAAUU, and both the antisense strand and the sense strand of the EGFR siRNA have thiolation modifications between the first three adjacent nucleotides at the 5' end and between the last three adjacent nucleotides at the 3' end;

[0895] Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, wherein the phosphate backbone between the last two nucleotides at the 3' end is thiolated;

[0896] Preferably, the positive strand of Survivin siRNA is: SEQ ID NO: 303: GCAGGUUCCUUAUCUGUCACA,

[0897] The antisense strand of Survivin siRNA is: SEQ ID NO: 300: UGUGACAGAUAAGGAACCUGCAG, wherein the phosphate backbone between the first three adjacent nucleotides at the 5' end is thiolated, and the phosphate backbone between the last three adjacent nucleotides at the 3' end is thiolated;

[0898] The sequence of the Her2 aptamer is:

[0899] SEQ ID NO: 194: AGCCGCGAGGGGAGGGAUAGGGUAGGGCGCGGCU, the phosphate backbone between the first two nucleotides at the 5' end has a thio modification; C or U has a 2'-F modification, and A or G has a 2'-OME modification.

[0900] Drug 64): Survivin siRNA-TFRA3 aptamer-AS1411 aptamer-3*AmiR-21-DNA vector, wherein the DNA vector is group 17) of the aforementioned 26 backbone sequence nucleic acid vectors, the TFRA3 aptamer is linked to the 5' end of sequence a via an AmiR-21, FA is linked to the 3' end of sequence a, the AS1411 aptamer is linked to the 5' end of sequence b via an AmiR-21, the sense strand of the survivin siRNA is linked to the 5' end of sequence c via an AmiR-21, and the antisense strand of the survivin siRNA is complementary and linked to the sense strand of the survivin siRNA;

[0901] Preferably, the sequence of the TFRA3 aptamer is: SEQ ID NO: 262: GCGTGGTCACACGC;

[0902] Preferably, the sequence of AmiR-21 is: GATAAGCT;

[0903] Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG;

[0904] Preferably, the sense strand of the Survivin siRNA is: SEQ ID NO: 304: GCAGGUUCCUUAUCUGUCA, wherein the phosphate backbone between the first three adjacent nucleotides at the 5' end is thiolated, the phosphate backbone between the last three adjacent nucleotides at the 3' end is thiolated, positions 7, 9-11 from the 5' end have 2'-F modifications, and the rest are 2'-OMe modifications;

[0905] The antisense strand of Survivin siRNA is: SEQ ID NO: 305: UGACAGAAUAAGGAACCUGCAGUU, with a thiolation modification between the 5' end and the first three positions of the 3' end, and 2'-F modifications at the 2nd, 6th, 8th, 9th, 12th, 14th, and 16th positions from the 5' end, and the rest are 2'-OMe modifications.

[0906] Drug 65): AS1411 aptamer-EGFR siRNA-VEGF165 aptamer-PD-L1 aptamer-RNA vector, wherein the RNA vector is group 16) of the aforementioned 26 backbone sequence nucleic acid vectors, the VEGF165 aptamer is linked to the 3' end of sequence a via a transition sequence AA, the PD-L1 aptamer is linked to the 3' end of sequence b via a transition sequence AA, the positive strand of the EGFR siRNA is linked to the 3' end of sequence c via a transition sequence AA, the AS1411 aptamer is linked to the 5' end of the antisense strand of the EGFR siRNA via a transition sequence AA, the antisense strand of the EGFR siRNA is complementary to the positive strand of the EGFR siRNA, and the first two nucleotides at the 5' end of sequence a of the DNA vector are independently thiolated;

[0907] Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, wherein the phosphate backbone between the first two nucleotides at the 5' end is thiolated;

[0908] Preferably, the sense strand of the EGFR siRNA is: SEQ ID NO: 82: CCUUAGCAGUCUUAUCUAAUU, wherein the phosphate backbone between the last three adjacent nucleotides at the 3' end is thiolated;

[0909] The antisense strand of EGFR siRNA is:

[0910] SEQ ID NO: 302: AAUUAGAUAAGACUGCUAAGGCA, the first three positions at the 5' end and the last three positions at the 3' end are both thiolated;

[0911] Preferably, the sequence of the VEGF165 aptamer is:

[0912] SEQ ID NO: 280: CGGAAUCAGUGAAUGCUUAUACAUCCG, wherein C and U have 2'-F modifications, A and G have 2'-OME modifications, and the phosphate backbone between the last two nucleotides at the 3' end has a thio modification;

[0913] Preferably, the sequence of the PD-L1 aptamer is:

[0914] SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, wherein C and U have 2'-F modification, A and G have 2'-OME modification, and the phosphate backbone between the last two nucleotides at the 3' end has a thio modification.

[0915] Drug 66): CEA aptamer-CD16a aptamer-Act-12c aptamer-PD-L1 aptamer-DNA vector, wherein the DNA vector is group 20) of the aforementioned 26 backbone sequence nucleic acid vectors, the CEA aptamer is connected to the 5' end of sequence a via a transition sequence AAA, the CD16a aptamer is connected to the 3' end of sequence a via a transition sequence AA, the Act-12c aptamer and the PD-L1 aptamer are each connected to the 5' end of sequence b and sequence c, respectively, via a transition sequence AA, and the first two nucleotides at the 3' end of sequence b and sequence c of the DNA vector are independently thiolated;

[0916] Preferably, the sequence of the CEA aptamer is: SEQ ID NO: 150: TTAACTTATTCGACCATA, wherein the phosphate backbone between nucleotides 1-2 at the 5' end is thiolated;

[0917] Preferably, the sequence of the CD16a aptamer is:

[0918] SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the phosphate backbone between the last 1-2 nucleotides at the 3' end is thiolated;

[0919] Preferably, the sequence of the Act-12c aptamer is:

[0920] SEQ ID NO: 137: CGGGGAAAGTCACGGGGGGTTTCAGATGTTCTGATCGGTGTGGAG, thiolation modification of the phosphate backbone between nucleotides 1 and 2 at the 5' end;

[0921] Preferably, the sequence of the PD-L1 aptamer is:

[0922] SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, a thiolation modification exists in the phosphate backbone between nucleotides 1 and 2 at the 5' end.

[0923] Drug 67): AS1411 aptamer-TAP siRNA-CD16a aptamer-CTLA-4 aptamer-DNA vector, wherein the DNA vector is group 14) of the aforementioned 26 backbone sequence nucleic acid vectors, the CD16a aptamer is linked to the 3' end of sequence a via the transition sequence AAAA, the CTLA-4 aptamer is linked to the 3' end of sequence b via the transition sequence AAAA, the sense strand of TAP siRNA is linked to the 3' end of sequence c via the transition sequence AAAA, the AS1411 aptamer is linked to the 5' end of the antisense strand of TAP siRNA via the transition sequence AAA, the antisense strand of TAP siRNA is complementary to the sense strand of TAP siRNA, and the first two nucleotides at the 5' end of sequence a, sequence b, and sequence c of the DNA vector are independently thiolated;

[0924] Preferably, the sequence of the AS1411 aptamer is:

[0925] SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, thiolation modification of the phosphate backbone between nucleotides 1 and 2 at the 5' end;

[0926] Preferably, the sense strand of the TAP siRNA is: SEQ ID NO: 301: GCUGCACACGGUUCAGAAU, wherein positions 1-3 of the 5' end and positions 1-3 of the 3' end are both thiolated, positions 7 and 9-11 of the 5' end are 2'-F modified, and the remaining nucleotides are 2'-OME modified;

[0927] The antisense strand of TAP siRNA is: SEQ ID NO: 109: AUUCUGAACCGUGUGCAGCUU, with 5' end 1-3 positions and 3' end 1-3 positions adjacent to each other having thiolation modifications, 5' end 2, 6, 8, 9, 12, 14, and 16 nucleotides having 2'-F modification, and the remaining nucleotides having 2'-OME modification;

[0928] Preferably, the sequence of the CD16a aptamer is:

[0929] SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, thiolation modifications are present between positions 1-2 at the 5' end and positions 1-2 at the end of the 3' end;

[0930] Preferably, the sequence of the CTLA-4 aptamer is:

[0931] SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU, the phosphate backbone between the last 1-2 nucleotides at the 3' end has a thio modification, C and U have 2'-F modification, and A and G have 2'-OME modification.

[0932] Drug 68): AS1411 aptamer-TAP siRNA-CD16a aptamer-Act-12c aptamer-DNA vector, wherein the DNA vector is group 14) of the aforementioned 26 backbone sequence nucleic acid vectors, the CD16a aptamer is linked to the 3' end of the a sequence via the transition sequence AAAA, the Act-12c aptamer is linked to the 3' end of the b sequence via the transition sequence AAAA, the sense strand of the TAP siRNA is linked to the 3' end of the c sequence via the transition sequence AAAA, the AS1411 aptamer is linked to the 5' end of the antisense strand of the TAP siRNA via the transition sequence AAA, the antisense strand of the TAP siRNA is complementary to the sense strand of the TAP siRNA, and the first two nucleotides at the 5' end of the a sequence, b sequence, and c sequence of the DNA vector are independently thiolated;

[0933] Preferably, the sequence of the AS1411 aptamer is:

[0934] SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, thiolation modification of the phosphate backbone between nucleotides 1 and 2 at the 5' end;

[0935] Preferably, the sense strand of the TAP siRNA is: SEQ ID NO: 301: GCUGCACACGGUUCAGAAU, wherein the phosphate backbone between adjacent nucleotides 1-3 at the 5' end and 1-3 at the 3' end has a thiolation modification, the nucleotides 7 and 9-11 from the 5' end have a 2'-F modification, and the remaining nucleotides have a 2'-OME modification;

[0936] The antisense strand of TAP siRNA is: SEQ ID NO: 109: AUUCUGAACCGUGUGCAGCUU, with thiolation modifications on the phosphate backbone between adjacent nucleotides 1-3 at the 5' end and 1-3 at the 3' end, 2'-F modifications on nucleotides 2, 6, 8, 9, 12, 14, and 16 from the 5' end, and 2'-OME modifications on the remaining nucleotides;

[0937] Preferably, the sequence of the CD16a aptamer is:

[0938] SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTG*G, the phosphate backbone between nucleotides 1 and 2 at the 3' end has a thiolation modification;

[0939] Preferably, the sequence of the Act-12c aptamer is:

[0940] SEQ ID NO: 137: CGGGGAAAGTCACGGGGGGTTTCAGATGTTCTGATCGGTGTGGAG, a thiolation modification exists in the phosphate backbone between the 1st and 2nd nucleotides at the 3' end.

[0941] Drug 69): CD16a aptamer-AS1411 aptamer-TAP siRNA-OX40 aptamer-Act-12c aptamer-DNA vector, wherein the DNA vector is group 14) of the aforementioned 26 backbone sequence nucleic acid vectors, wherein the CD16a aptamer is linked to the 5' end of the a sequence via the transition sequence AA, the sense strand of the TAP siRNA is linked to the 3' end of the a sequence via the transition sequence AA, the AS1411 aptamer is linked to the 5' end of the antisense strand of the TAP siRNA via the transition sequence AAA, the antisense strand of the TAP siRNA is complementary to the sense strand of the TAP siRNA, the OX40 aptamer is linked to the 3' end of the b sequence via the transition sequence AA, and the Act-12c aptamer is linked to the 5' end of the c sequence via the transition sequence AAAA, and the first two nucleotides at the 5' end of the b sequence and the c sequence of the DNA vector are independently thiolated;

[0942] Preferably, the sequence of the CD16a aptamer is:

[0943] SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the phosphate backbone between nucleotides 1 and 2 at the 5' end has a thiolation modification;

[0944] Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, wherein the phosphate backbone between nucleotides 1-2 at the 5' end is thiolated;

[0945] Preferably, the sense strand of the TAP siRNA is: SEQ ID NO: 301: GCUGCACACGGUUCAGAAU, wherein the phosphate backbone between adjacent nucleotides 1-3 at the 5' end and 1-3 at the 3' end has a thiolation modification, nucleotides 7, 9, 10, and 11 from the 5' end have a 2'-F modification, and the remaining nucleotides have a 2'-OME modification;

[0946] The antisense strand of TAP siRNA is: SEQ ID NO: 109: AUUCUGAACCGUGUGCAGCUU, with thiolation modifications on the phosphate backbone between adjacent nucleotides 1-3 at the 5' end and 1-3 at the 3' end, 2'-F modifications on nucleotides 2, 6, 8, 9, 12, 14, and 16 from the 5' end, and '-OME modifications on the remaining nucleotides;

[0947] Preferably, the sequence of the OX40 aptamer is:

[0948] SEQ ID NO: 228: GGGAGGACGAUGCGGCAGUCUGCAUCGUAGGAAUCGCCACCGUAUACUUUCCCACCAGACGACUCGCUG, the phosphate backbone between nucleotides 1 and 2 at the 3' end has a thio modification, C and U have 2'-F modifications, and A and G have 2'-OMe modifications;

[0949] Preferably, the sequence of the Act-12c aptamer is:

[0950] SEQ ID NO: 137: CGGGGAAAGTCACGGGGGGTTTCAGATGTTCTGATCGGTGTGGAG, with thiolation modifications at positions 1-2 of the 5' end.

[0951] Drug 70): CTLA-4 aptamer-CD40 aptamer-FAP aptamer-DNA vector, wherein the DNA vector is group 15) of the aforementioned 26 backbone sequence nucleic acid vectors, the CTLA-4 aptamer is linked to the 5' end of sequence a via the transition sequence TTTTT, the CD40 aptamer is linked to the 5' end of sequence b via the transition sequence TTTTT, and the FAP aptamer is linked to the 5' end of sequence c via the transition sequence TTTTT, and the first two nucleotides at the 3' end of sequence a, sequence b, and sequence c of the DNA vector independently have a thiolation modification;

[0952] Preferably, the sequence of the CTLA-4 aptamer is:

[0953] SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU, the phosphate backbone between nucleotides 1-2 at the 5' end has a thio modification, C and U have 2'-F modifications, and A and G have 2'-OMe modifications;

[0954] Preferably, the sequence of the CD40 aptamer is:

[0955] SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the phosphate backbone between nucleotides 1 and 2 at the 5' end is thiolated;

[0956] Preferably, the sequence of the FAP aptamer is:

[0957] SEQ ID NO: 188: CCGCTCGAGCTAGTCTGACAAAGAGAAACAC, the phosphate backbone between nucleotides 1 and 2 at the 5' end is thio-modified.

[0958] Drug 71): VEGF165 aptamer-ASAP1 siRNA-CD24A-2 aptamer-SARS-CoV-2-N48 aptamer-DNA vector, wherein the DNA vector is group 14) of the aforementioned 26 backbone sequence nucleic acid vectors, the positive strand of ASAP1 siRNA is linked to the 3' end of the c sequence via a transition sequence AA, the VEGF165 aptamer is linked to the 5' end of the antisense strand of ASAP1 siRNA via a transition sequence AA, the antisense strand of ASAP1 siRNA is complementary to the positive strand of ASAP1 siRNA, the CD24 A-2 aptamer is linked to the 3' end of the b sequence via a transition sequence AA, the SARS-CoV-2-N48 aptamer is linked to the 3' end of the a sequence via a transition sequence AA, and the first two nucleotides at the 5' end of the b sequence and the c sequence of the DNA vector are independently thiolated;

[0959] Preferably, the sequence of the VEGF165 aptamer is:

[0960] SEQ ID NO: 280: CGGAAUCAGUGAAUGCUUAUACAUCCG, the phosphate backbone between nucleotides 1 and 2 at the 5' end has a thio modification, C and U have 2'-F modifications, and A and G have 2'-OME modifications;

[0961] Preferably, the antisense strand of the ASAP1 siRNA is: SEQ ID NO: 65: UGAUAUUAUGGAAGCAAAUUU, the phosphate backbone between nucleotides 1-3 at the 5' end and 1-3 at the 3' end has a thio modification, nucleotides 2, 6, 8, 9, 12, 14, and 16 at the 5' end have a 2'-F modification, and the rest are 2'-OME modifications;

[0962] The positive strand of ASAP1 siRNA is: SEQ ID NO: 64: AUUUGCUUCCAUAAUAUCAUU, with thiolation modifications on the phosphate backbone between nucleotides 1-3 at the 5' end and 1-3 at the 3' end, 2'-F modifications on nucleotides 7 and 9-11 at the 5' end, and 2'-OME modifications on the rest;

[0963] Preferably, the sequence of the SARS-CoV-2-N48 aptamer is:

[0964] SEQ ID NO: 222: GCTGGATGTCGCTTACGACAATATTCCTTAGGGGCACCGCTACATTGACACATCCAGC, the phosphate backbone between nucleotides 1 and 2 at the 3' end has a thiolation modification;

[0965] Preferably, the sequence of the CD24A-2 aptamer is:

[0966] SEQ ID NO: 167: ATCCAGAGTGACGCAGCATATGTGGGTGGGTGGGCGGTTATGCTGAGTCAGCCTTGCTTGGACACGGTGGCTTAGT, the phosphate backbone between the first and second nucleotides at the 5' end is thiolated.

[0967] Drug 72): 3*FGF5 aptamer-DNA vector, wherein the DNA vector is group 15) of the aforementioned 26 backbone sequence nucleic acid vectors, the three FGF5 aptamers are each linked to the 5' end of sequence a, the 5' end of sequence b, and the 5' end of sequence c via U, and the first two nucleotides at the 3' end of sequence a, sequence b, and sequence c of the DNA vector are independently thiolated;

[0968] Preferably, the sequence of the FGF5 aptamer is:

[0969] SEQ ID NO: 186: GGGCGACCUCUCCGUACUGACCUACAGAGCGACAUACUAGUGUAUCCAGAUCGCCC; the phosphate backbone between the 1st and 2nd nucleotides at the 5' end has a thio modification, C and U have 2'-F modification, and A and G have 2'-OMe modification.

[0970] Drug 73): AS1411 aptamer-ASAP1 siRNA-VEGF aptamer-SARS-CoV-2-N48 aptamer-RNA vector, wherein the DNA vector is the 21st group of nucleic acid vectors with the aforementioned 26 backbone sequences, the VEGF aptamer is connected to the 3' end of the a sequence via the transition sequence AA, the SARS-CoV-2-N48 aptamer is connected to the 3' end of the b sequence via the transition sequence AA, the positive strand of the ASAP1 siRNA is connected to the 3' end of the c sequence, and the AS1411 aptamer is connected to the 5' end of the antisense strand of the ASAP1 siRNA via the transition sequence AA, and the antisense strand of the ASAP1 siRNA is complementary to the positive strand of the ASAP1 siRNA; the first two nucleotides at the 5' end of the a sequence, b sequence, and c sequence of the DNA vector are independently thiolated, and A and G in the c sequence have 2'-OME modifications, and C and U have 2'-F modifications;

[0971] Preferably, the sequence of the AS1411 aptamer is:

[0972] SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, the phosphate backbone between the 1st and 2nd nucleotides at the 5' end is thiolated;

[0973] Preferably, the antisense strand of the ASAP1 siRNA is: SEQ ID NO: 65: UGAUAUUAUGGAAGCAAAUUU, wherein the phosphate backbones at positions 1-3 of the 5' end and between adjacent nucleotides 1-3 of the 3' end have thiolation modifications, positions 2, 6, 8, 9, 12, 14, and 16 from the 5' end have 2'-F modifications, and the rest have 2'-OME modifications;

[0974] The sense strand of ASAP1 siRNA is: SEQ ID NO: 64: AUUUGCUUCCAUAAUAUCAUU, with thiolation modifications on the phosphate backbone between adjacent nucleotides 1-3 at the 5' end and 1-3 at the 3' end;

[0975] Preferably, the sequence of the VEGF aptamer is: SEQ ID NO: 280: CGGAAUCAGUGAAUGCUUAUACAUCCG, C and U have 2'-F modifications, and A and G have 2'-OMe modifications;

[0976] Preferably, the sequence of the SARS-CoV-2-N48 aptamer is:

[0977] SEQ ID NO: 222: GCTGGATGTCGCTTACGACAATATTCCTTAGGGGCACCGCTACATTGACACATCCAGC, the phosphate backbone between the 1st and 2nd nucleotides at the 3' end is thio-modified.

[0978] Drug 74): CpG2006-CD40 aptamer-PD1 aptamer-DNA vector, wherein the DNA vector is the nucleic acid vector of group 6) among the aforementioned 26 backbone sequences, CpG2006 is connected to the 5' end of sequence a via a transition sequence, the CD40 aptamer is connected to the 5' end of sequence b via a transition sequence, and the PD-1 aptamer is connected to the 5' end of sequence c via a transition sequence;

[0979] Preferably, the sequence of CpG2006 is:

[0980] SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, there is a thio modification in the phosphate backbone between adjacent nucleotides;

[0981] Preferably, the sequence of the CD40 aptamer is:

[0982] SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the ribose 2-position of the first 4 nucleotides from the 5' end has an MOE modification, and the phosphate backbone between the first 5 nucleotides from the 5' end has a thiolation modification;

[0983] Preferably, the sequence of the PD1 aptamer is:

[0984] SEQ ID NO: 254: ACCGACAGTGAAGGACTCAGCGAACTCTCAGACTCGGTTC, the 2-position of the ribose of the first 4 nucleotides from the 5' end has an MOE modification, and the phosphate backbone between the first 5 nucleotides from the 5' end has a thiolation modification.

[0985] Drug 75): CD24 aptamer-CpG2006 variant-CD40 aptamer-PD-L1 aptamer-DNA vector, wherein the DNA vector is the 6th group of nucleic acid vectors with the aforementioned 26 backbone sequences, the CD24 aptamer is linked to the 5' end of sequence a via the CpG2006 variant sequence GTCGTT, the CD40 aptamer is linked to the 5' end of sequence b via the transition sequence TTTTT, and the PD-L1 aptamer is linked to the 5' end of sequence c via the transition sequence TTTTT;

[0986] Preferably, the sequence of the CD24 aptamer is:

[0987] SEQ ID NO: 166: TATGTGGGTGGGTGGGCGGTTATGCTGAGTCAGCCTTGCT, the phosphate backbone of the first 4 nucleotides at the 5' end is thiolated;

[0988] Preferably, the sequence of the CD40 aptamer is:

[0989] SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the phosphate backbone between the first five nucleotides at the 5' end is thiolated;

[0990] Preferably, the sequence of the PD-L1 aptamer is:

[0991] SEQ ID NO: 238: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGG, the ribose of the first 6 nucleotides at the 5' end has a 2'-O-MOE modification;

[0992] The transition sequence TTTTT is PEG-modified TTTTT.

[0993] Drug 76): HBsAg aptamer-HBV siRNA-miR-34-PD-L1 aptamer-miR-542-AS1411 aptamer-DNA vector, wherein the DNA vector is the 24th group of nucleic acid vectors of the aforementioned 26 backbone sequences, the positive strand of the HBV siRNA is connected to the 3' end of the a sequence, the HBsAg aptamer is connected to the antisense strand of the HBV siRNA and is located at the 5' end of the antisense strand of the HBV siRNA, the PD-L1 aptamer is connected to the 3' end of the b sequence via miR-34, and the AS1411 aptamer is connected to the 3' end of the c sequence via miR-542;

[0994] Preferably, the sense strand of the HBV siRNA is: SEQ ID NO: 88: GGACUUCUCUCAAUUUUCUUU, and the antisense strand is: SEQ ID NO: 89: AGAAAAUUGAGAGAAGUCCUU, wherein the C and U in the sense and antisense strands of the HBV siRNA have 2'-F modifications, and the phosphate backbone between the 1st to 3rd nucleotides at the 3' end has phosphothioate modifications;

[0995] Preferably, the sequence of the HBsAg aptamer is:

[0996] SEQ ID NO: 192: CACAGCGAACAGCGGCGGACATAATAGTGCTTACTACGAC, the first four nucleotide phosphate backbones at the 5' end are thiolated;

[0997] Preferably, the sequence of miR-34 is: TGTGACAAG;

[0998] Preferably, the sequence of the PD-L1 aptamer is:

[0999] SEQ ID NO: 238: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGG, 2'-O-MOE modification on the ribose of the 3'-nucleotide at the 3' end;

[1000] Preferably, the sequence of miR-542 is: TGGCAGTGT;

[1001] Preferably, the sequence of the AS1411 aptamer is:

[1002] SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, a 2'-O-MOE thio modification is present on the phosphate backbone between the 4 nucleotides at the 3' end.

[1003] Drug 77): IL-4Ra aptamer-TIMC-d aptamer-4*miR-126-RNA vector, wherein the RNA vector is the 25th group of nucleic acid vectors of the aforementioned 26 backbone sequences, the IL-4Ra aptamer is directly linked to the 5' end of sequence a, the TIMC-d aptamer is directly linked to the 5' end of sequence b, and four miR-126s are serially linked to the 5' end of sequence c.

[1004] The sequence of the IL-4Ra aptamer is:

[1005] SEQ ID NO: 203: AAAAAGCAACAGGGUGCUCCAUGCGCAUGGAACCUGCGCG, the first four nucleotide phosphate backbones at the 5' end are thiolated;

[1006] The sequence of the TIMC-d aptamer is:

[1007] SEQ ID NO: 272: AAGCAACACCUUAGUCGCGAUUGAUACGUGCGCAGUCAU, the first four nucleotide phosphate backbones at the 5' end are thiolated;

[1008] The sequence of miR-126 is:

[1009] UCGUACC, there is a thiolation modification on the phosphate backbone between adjacent nucleotides.

[1010] Drug 78): CD3-4 aptamer-PD-1 aptamer-BCMA aptamer-DNA vector, wherein the DNA vector is group 24) of the aforementioned 26 backbone sequence nucleic acid vectors, and the CD3-4 aptamer is linked to the complementary sequence A' of the single-stranded connecting bridge sequence A in the a sequence via the transition sequence TTTTTT, and is further linked to the 3' end of the a sequence via the complementary pairing of the complementary sequence A' and the single-stranded connecting bridge sequence A;

[1011] The PD-1 aptamer is connected to the complementary sequence B' of the single-stranded bridge sequence B in the b sequence through the transition sequence TTTTT, and is connected to the 3' end of the b sequence through the complementary pairing of the complementary sequence B' and the single-stranded bridge sequence B;

[1012] The BCMA aptamer is connected to the complementary sequence C' of the single-stranded connecting bridge sequence C in the c sequence, and is connected to the 3' end of the c sequence through the complementary pairing of the complementary sequence C' and the single-stranded connecting bridge sequence C;

[1013] The sequence a is:

[1014] SEQ ID NO: 15: GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC, wherein the underlined portion is the single-stranded connecting bridge sequence A;

[1015] Preferably, the sequence of the complementary sequence A' of the CD3-4 aptamer-transition sequence-single-stranded bridge sequence A is:

[1016] SEQ ID NO: 306: TCTCGGACGCGTGTGGTCGGCCGAGTGGCCCACGGTAGAAGGGTTAGAACTGCTGGTTGGTGAATCTCGCTGCCTGGCCCTAGAGTGTTTTTTGCCACCGTGCTACA;

[1017] The b sequence in the DNA vector is:

[1018] SEQ ID NO: 16: CCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, wherein the underlined portion is the single-stranded connecting bridge sequence B;

[1019] Preferably, the sequence of the complementary sequence B' of the PD-1 aptamer-transition sequence TTTTT-single-stranded bridge sequence B is:

[1020] SEQ ID NO: 307: ACCGACAGTGAAGGACTCAGCGAACTCTCAGACTCGGTTCTTTTTCACGGCCGCGCCGA; the phosphate backbone between the first five nucleotides at the 5' end is thiolated;

[1021] The c sequence is: SEQ ID NO: 17: GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG, wherein the underlined portion is the single-stranded connecting bridge sequence C;

[1022] Preferably, the BCMA aptamer-transition sequence U-complementary sequence C' of the single-stranded connecting bridge sequence C is as follows: SEQ ID NO: 308: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUACUCAGCAGCAGCAGCA, the underlined portion is the complementary sequence C' of the single-stranded connecting bridge sequence C, the phosphate backbone between the three nucleotides at the 3' end has a thiolation modification, the ribose of the first four nucleotides at the 5' end has a 2'-O-MOE modification, and the C and U of the remaining nucleotides have a 2'F modification.

[1023] Drug 79): CpG2006-CD38 aptamer-PD-L1 aptamer-DNA vector; wherein the DNA vector is the 6th group of nucleic acid vectors of the aforementioned 26 backbone sequences, CpG2006 is connected to the 5' end of sequence a via the transition sequence TTTTT, the CD38 aptamer is connected to the 5' end of sequence b via the transition sequence TTTTT, and the PD-L1 aptamer is connected to the 5' end of sequence c via the transition sequence TTTTT.

[1024] Preferably, the CpG2006-transition sequence TTTTT-a sequence is:

[1025] SEQ ID NO: 309: TCGTCGTTTTGTCGTTTTGTCGTTTTTTTGCGACGCCCACGAGCGTTCCGGGAGAGGAGC, the phosphate backbone of the adjacent nucleotide of CpG2006 has a thio modification;

[1026] Preferably, the CD38 aptamer-transition sequence TTTTT-b sequence is:

[1027] SEQ ID NO: 310: TACGTGAATCTCGTACGATACTCTGTAAGCGTTTTTTGCTCCTCTCCCGGTTCGCCGCGAGCCGCG, the ribose sugars of the first three nucleotides at the 5' end have a 2'-O-MOE modification;

[1028] Preferably, the PD-L1 aptamer-transition sequence TTTTT-c sequence is:

[1029] SEQ ID NO: 311: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGGTTTTTCGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the ribose sugars of the first 6 nucleotides at the 5' end have 2'-O-MOE modifications.

[1030] Drug 80): CD20 aptamer-CpG-BYZD-CD38 aptamer-miR-34-CD3 aptamer-DNA vector; wherein the DNA vector is the sixth group of nucleic acid vectors with the aforementioned 26 backbone sequences, the CD20 aptamer is linked to the 5' end of sequence a via CpG-BYZDAGCGAA, the CD38 aptamer is linked to the 5' end of sequence b via miR-34, and the CD3 aptamer is linked to the 5' end of sequence c via the transition sequence TTTTT.

[1031] Preferably, the CD20 aptamer-CpG-BYZD-a sequence is:

[1032] SEQ ID NO: 312: TGCGTGTGTCTGTTTTTTATCTTCTTTTATCTACTCTTAGGGATTTGGGCGGAGCGAAGCGACGCCCACGAGCGTTCCGGGAGAGGAGC, SEQ ID NO: 165: TGCGTGTTGTAGTGTGTCTGTTTTTTATCTTCTTTTATCTACTCTTAGGGATTTGGGCGG is a CD20 aptamer, AGCGAA is CpG-BYZD, and the phosphate backbone between the first four nucleotides at the 5' end has a thiolation modification;

[1033] Preferably, the CD38 aptamer-miR-34-b sequence is:

[1034] SEQ ID NO: 313: TACGTGAATCTCGTACGATACTCTGTAAGCGTTGTGACAGGCTCCTCTCCCGGTTCGCCGCGAGCCGCG, 2'-O-MOE modification on the ribose of the first 3 nucleotides at the 5' end, TGTGACAAG represents miR-34, the sequence before TGTGACAAG is the CD38 aptamer, and the sequence after TGTGACAAG is the b sequence;

[1035] Preferably, the CD3 aptamer-transition sequence TTTTT-c sequence is:

[1036] SEQ ID NO: 314: GCCGCGGGGTGGGTCTAGTGTGGATGTTTAGGGGGCGGCTTTTTCGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, 2'-O-MOE modification exists on the ribose sugars of the first 4 nucleotides at the 5' end.

[1037] Drug 81): CpG2006-CD38 aptamer-miR-126-PD-L1 aptamer-DNA vector; wherein the DNA vector is the 6th group of nucleic acid vectors of the aforementioned 26 backbone sequences, CpG2006 is connected to the 5' end of sequence a via the transition sequence TTTTT, the CD38 aptamer is connected to the 5' end of sequence b via miR-126, and the PD-L1 aptamer is connected to the 5' end of sequence c via the transition sequence TTTTT.

[1038] Preferably, the CpG2006-transition sequence TTTTT-a sequence is:

[1039] SEQ ID NO: 309: TCGTCGTTTTGTCGTTTTGTCGTTTTTTTGCGACGCCCACGAGCGTTCCGGGAGAGGAGC, a thioate modification exists on the phosphate backbone between adjacent nucleotides of CpG2006, and a thioate modification exists on the phosphate backbone between the two nucleotides at the 3' end of the a sequence;

[1040] Preferably, the CD38 aptamer-miR-126-b sequence is:

[1041] SEQ ID NO: 315: TACGTGAATCTCGTACGATACTCTGTAAGCGTUCGUACCGGCTCCTCTCCCGGTTCGCCGCGAGCCGCG, wherein the sequence of the CD38 aptamer is SEQ ID NO: 170: TACGTGAATCTCGTACGATACTCTGTAAGCGT, and the ribose of the first three nucleotides at the 5' end has a 2'-O-MOE modification; UCGUACCG is the sequence of miR-126, and the ribose of each nucleotide has a 2'-O-MOE modification;

[1042] Preferably, the PD-L1 aptamer-transition sequence TTTTT-c sequence is:

[1043] SEQ ID NO: 311: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGGTTTTTCGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the ribose of the first 6 nucleotides at the 5' end of the PD-L1 aptamer has a 2'-O-MOE modification.

[1044] Drug 82): BCMA aptamer-miR-126-CD38 aptamer-miR-122-CD3 aptamer-miR-34-DNA vector; wherein the DNA vector is the nucleic acid vector of group 6) among the aforementioned 26 backbone sequences, the BCMA aptamer is linked to the 5' end of sequence a via miR-126, the CD38 aptamer is linked to the 5' end of sequence b via miR-122, and the CD3 aptamer is linked to the 5' end of sequence c via miR-34;

[1045] Preferably, the BCMA aptamer-miR-126-a sequence is:

[1046] SEQ ID NO: 316: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUACUCGTACCGGCGACGCCCACGAGCGTTCCGGGAGAGGAGC, wherein CGTACCG is the sequence of miR-126, the sequence before CGTACCG is the sequence of the BCMA aptamer, and the sequence after CGTACCG is an a sequence, the ribose of the first four nucleotides at the 5' end of the BCMA aptamer sequence has a 2'-O-MOE residue, and the C and U residues at the remaining positions have a 2'F modification;

[1047] Preferably, the CD38 aptamer-miR-122-b sequence is:

[1048] SEQ ID NO: 317: TmAmCmGTGAATCTCGTACGATACTCTGTAAGCGTGGAAGTGTGCTCCTCTCCCGGTTC GCCGCGAGCCGCG, the ribose of the first three nucleotides at the 5' end has a 2'-O-MOE modification, GGAAGTGT is the sequence of miR-122, the sequence before GGAAGTGT is the sequence of the CD38 adaptor, and the sequence after GGAAGTGT is the b sequence,

[1049] Preferably, the CD3 aptamer-miR-34-c sequence is:

[1050] SEQ ID NO: 318: AmGmCmCmGCGGGGTGGGTCTAGTGTGGATGTTTAGGGGGCGGCTTGTGACAGCGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the ribose of the first 4 nucleotides at the 5' end has a 2'-O-MOE modification, TGTGACA is the sequence of miR-34, the sequence before TGTGACA is the sequence of the CD3 adaptor, and the sequence after TGTGACA is the c sequence.

[1051] Drug 83): GPC3 aptamer-AmiR-21-CD38 aptamer-miR-122-PD-L1 aptamer-miR-34-DNA vector; wherein the DNA vector is the 6th group of nucleic acid vectors with the aforementioned 26 backbone sequences, the GPC3 aptamer is linked to the 5' end of sequence a via AmiR-21, the CD38 aptamer is linked to the 5' end of sequence b via miR-122, and the PD-L1 aptamer is linked to the 5' end of sequence c via miR-34;

[1052] Preferably, the GPC3 aptamer-AmiR-21-a sequence is: SEQ ID NO: 319: TAACGCTGACCTTAGCTGCATGGCTTTACATGTTCCAGATAAGCTGCGACGCCCACGAGCGTTCCGGGAGAGGAGC, the phosphate backbone between the first four nucleotides at the 5' end has a thiolation modification, GATAAGCT is the sequence of AmiR-21, the sequence before GATAAGCT is the sequence of the GPC3 aptamer, and the sequence after GATAAGCT is the a sequence;

[1053] Preferably, the CD38 aptamer-miR-122-b sequence is: SEQ ID NO: 317: TACGTGAATCTCGTACGATACTCTGTAAGCGTGGAAGTGTGCTCCTCTCCCGGTTCGCCGCGAGCCGCG, wherein the phosphate backbone between the first four nucleotides at the 5' end has a thiolation modification; GGAAGTGT is the sequence of miR-122, the sequence before GGAAGTGT is the sequence of the CD38 aptamer, and the sequence after GGAAGTGT is the b sequence;

[1054] Preferably, the PD-L1 aptamer-miR-34-c sequence is: SEQ ID NO: 320: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGGTGTGACAGCGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the ribose of the first 6 nucleotides at the 5' end has a 2'-O-MOE modification; TGTGACAAG is the sequence of miR-34, the sequence before TGTGACAAG is the sequence of the PD-L1 aptamer, and the sequence after TGTGACAAG is the c sequence.

[1055] Drug 84): CpG2006-VEGF165 aptamer-miR-122-PD-L1 aptamer-DNA vector; wherein the DNA vector is the nucleic acid vector of group 6) among the aforementioned 26 backbone sequences, CpG2006 is linked to the 5' end of sequence a via the transition sequence TTTTT, the VEGF165 aptamer is linked to the 5' end of sequence b via miR-122, and the PD-L1 aptamer is linked to the 5' end of sequence c via the transition sequence TTTTT;

[1056] Preferably, the CpG2006-transition sequence TTTTT-a sequence is:

[1057] SEQ ID NO: 309: TCGTCGTTTTGTCGTTTTGTCGTTTTTTTGCGACGCCCACGAGCGTTCCGGGAGAGGAGC; the phosphate backbone between adjacent nucleotides of CpG2006 has a thio modification;

[1058] Preferably, the VEGF165 aptamer-miR-122-b sequence is:

[1059] SEQ ID NO: 321: CGGAAUCAGUGAAUGCUUAUACAUCCGGGAAGTGTGCTCCTCTCCCGGTTCGCCGCGAGCCGCG, the ribose of the first four nucleotides at the 5' end has a 2'-O-MOE modification, and the C and U in the remaining RNA have a 2'F modification; GGAAGTGT is the sequence of miR-122, the sequence before GGAAGTGT is the sequence of the VEGF165 aptamer, and the sequence after GGAAGTGT is the b sequence;

[1060] Preferably, the PD-L1 aptamer-transition sequence TTTTT-c sequence is:

[1061] SEQ ID NO: 311: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGGTTTTTCGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the ribose sugars of the first 6 nucleotides at the 5' end have 2'-O-MOE modifications.

[1062] Drug 85): CpG2006-HBsAg aptamer-miR-122-PD-L1 aptamer-DNA vector; wherein the DNA vector is the nucleic acid vector of group 6) among the aforementioned 26 backbone sequences, CpG2006 is linked to the 5' end of sequence a via the transition sequence TTTTT, the HBsAg aptamer is linked to the 5' end of sequence b via miR-122, and the PD-L1 aptamer is linked to the 5' end of sequence c via the transition sequence TTTTT;

[1063] Preferably, the CpG2006-transition sequence TTTTT-a sequence is:

[1064] SEQ ID NO: 309: TCGTCGTTTTGTCGTTTTGTCGTTTTTTTGCGACGCCCACGAGCGTTCCGGGAGAGGAGC; the phosphate backbone between adjacent nucleotides of CpG2006 has a thio modification;

[1065] Preferably, the HBsAg aptamer-miR-122-b sequence is:

[1066] SEQ ID NO: 322: CACAGCGAACAGCGGCGGACATAATAGTGCTTACTACGACGGAAGTGTGCTCCTCTCCCGGTTCGCCGCGAGCCGCG, the phosphate backbone between the first four nucleotides at the 5' end has a thiolation modification; GGAAGTGT is the sequence of miR-122, the sequence before GGAAGTGT is the sequence of the HBsAg aptamer, and the sequence after GGAAGTGT is the b sequence;

[1067] Preferably, the PD-L1 aptamer-transition sequence TTTTT-c sequence is:

[1068] SEQ ID NO: 311: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGGTTTTTCGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the ribose sugars of the first 6 nucleotides at the 5' end have 2'-O-MOE modifications.

[1069] Drug 86): ASO-GSK836-HBsAg aptamer-miR-122-PD-L1 aptamer-DNA vector; wherein the DNA vector is the nucleic acid vector of group 6) among the aforementioned 26 backbone sequences, ASO-GSK836 is connected to the 5' end of sequence a via the transition sequence TTTTT, the HBsAg aptamer is connected to the 5' end of sequence b via miR-122, and the PD-L1 aptamer is connected to the 5' end of sequence c via the transition sequence TTTTT;

[1070] Preferably, the sequence of ASO-GSK836-transition sequence TTTTT-a is:

[1071] SEQ ID NO: 323: GCAGAGGTGAAGCGAAGTCGTTTTTGCGACGCCCACGAGCGTTCCGGGAGAGGAGC, the phosphate backbone between the adjacent nucleotides at the first 6 nucleotides of the 5' end has a thiolation modification;

[1072] Preferably, the HBsAg aptamer-miR-122-b sequence is:

[1073] SEQ ID NO: 322: CACAGCGAACAGCGGCGGACATAATAGTGCTTACTACGACGGAAGTGTGCTCCTCTCCCGGTTCGCCGCGAGCCGCG, the phosphate backbone between the first four nucleotides at the 5' end has a thiolation modification; GGAAGTGT is the sequence of miR-122, the sequence before GGAAGTGT is the sequence of the HBsAg aptamer, and the sequence after GGAAGTGT is the b sequence;

[1074] Preferably, the PD-L1 aptamer-transition sequence TTTTT-c sequence is:

[1075] SEQ ID NO: 311: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGGTTTTTCGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the ribose sugars of the first 6 nucleotides at the 5' end have 2'-O-MOE modifications.

[1076] Drug 87): BCMA aptamer-CD38 aptamer-miR-126-PD-L1 aptamer-miR-34-DNA vector; wherein the DNA vector is the nucleic acid vector of group 6) among the aforementioned 26 backbone sequences, the BCMA aptamer is directly linked to the 5' end of sequence a, the CD38 aptamer is linked to the 5' end of sequence b via miR-126, and the PD-L1 aptamer is linked to the 5' end of sequence c via miR-34;

[1077] Preferably, the BCMA aptamer-a sequence is:

[1078] SEQ ID NO: 324: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUACUUGCGACGCCCACGAGCGTTCCGGGAGAGGAGC, wherein, SEQ ID NO: 140: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUAC is a BCMA aptamer in RNA form, all nucleotides of the RNA have 2'-F modifications, and the rest are alpha sequences,

[1079] Preferably, the CD38 aptamer-miR-126-b sequence is:

[1080] SEQ ID NO: 325: TACGTGAATCTCGTACGATACTCTGTAAGCGTGTCGTTGCTCCTCTCCCGGTTCGCCGCGAGCCGCG, the phosphate backbone between the first four nucleotides at the 5' end has a thiolation modification, GTCGTT is the sequence of miR-126, the sequence before GTCGTT is the CD38 aptamer, and the sequence after GTCGTT is the b sequence;

[1081] Preferably, the PD-L1 aptamer-miR-34-c sequence is:

[1082] SEQ ID NO: 320: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGGTGTGACAGCGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the ribose of the first 6 nucleotides at the 5' end has a 2'-O-MOE modification, TGTGACAAG is the sequence of miR-34, the sequence before TGTGACAAG is the sequence of the PD-L1 adaptor, and the sequence after TGTGACAAG is the c sequence.

[1083] Drug 88): AS1411 aptamer-FGF2 aptamer-3*AmiR-21-DNA vector; the AS1411 aptamer is linked to the 5' end of the DNA vector sequence a via the transition sequence TTTTT, the FGF2 aptamer is linked to the 5' end of the DNA vector sequence b via the transition base U, and the three AmiR-21s are directly linked in series to the 5' end of the DNA vector sequence c.

[1084] Preferably, the AS1411 aptamer-transition sequence TTTTT-a sequence is:

[1085] SEQ ID NO: 326: GGTGGTGGTGGTTGTGGTGGTGGTGGTTTTTGCGCCCACGAGCGTTCCGGGAGAGC;

[1086] Preferably, the FGF2 aptamer-transition base Ub sequence is: SEQ ID NO: 327: GGGAUACUAGGGCAUUAAUGUUACCAGUGUAGUCCCUCCCUGCTCTCCCGGTTCGCCGCCAGCCGCC, wherein SEQ ID NO: 183: GGGAUACUAGGGCAUUAAUGUUACCAGUGUAGUCCC is an FGF2 aptamer in RNA form, wherein the C and U bases in the RNA have 2'-F modifications, and the rest are b sequences;

[1087] Preferably, the 3*AmiR-21-c sequence is:

[1088] SEQ ID NO: 328: GATAAGCTGATAAGCTGATAAGCTGGCGGCAGGCGGCCATAGCCGTGGGCGC, where GATAAGCT is the sequence of AmiR-21, and the phosphate backbone of the adjacent nucleotides has a thio modification.

[1089] Drug 89): HBsAg aptamer-CD40 aptamer-PD-L1 aptamer-DNA vector, the HBsAg aptamer is connected to the 5' end of the DNA vector sequence a through the transition sequence TTTTT, the CD40 aptamer is connected to the 5' end of the DNA vector sequence b through the transition sequence TTTTT, and the PD-L1 aptamer is connected to the 5' end of the DNA vector sequence c through the transition sequence TTTTT.

[1090] Preferably, the HBsAg aptamer-transition sequence TTTTT-a sequence is:

[1091] SEQ ID NO: 329: CACAGCGAACAGCGGCGGACATAATAGTGCTTACTACGACTTTTTGCGACGCCCACGAGCGTTCCGGGAGAGGAGC, the phosphate backbone of the first four nucleotides at the 5' end has a thiolation modification, the sequence before the transition sequence TTTTT is the sequence of the HBsAg aptamer, and the sequence after the transition sequence TTTTT is the a sequence;

[1092] Preferably, the CD40 aptamer-transition sequence TTTTT-b sequence is:

[1093] SEQ ID NO: 330: CCAACGAGTAGGCGATAGCGCGTGGTTTTTGCTCCTCTCCCGGTTCGCCGCGAGCCGCG, the phosphate backbone between the first 3 nucleotides at the 5' end and the first 3 nucleotides at the 3' end has thio modifications, the sequence before the transition sequence TTTTT is the CD40 aptamer sequence, and the sequence after the transition sequence TTTTT is sequence b;

[1094] Preferably, the PD-L1 aptamer-transition sequence TTTTT-c sequence is:

[1095] SEQ ID NO: 331: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGTTTTTTCGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the phosphate backbone between the first 3 nucleotides at the 5' end and the first 3 nucleotides at the 3' end has a thiolation modification, the sequence before the transition sequence TTTTT is the sequence of the PD-L1 adaptor, and the sequence after the transition sequence TTTTT is the c sequence.

[1096] Drug 90): HBsAg aptamer-CD40 aptamer-PD-L1 aptamer-DNA vector. Compared with drug 89), except for the sequence of the PD-L1 aptamer, the rest are the same. Among them, the sequence of the PD-L1 aptamer-transition sequence TTTTT-c is:

[1097] SEQ ID NO: 311: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGGTTTTTCGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the ribose of the first 6 nucleotides at the 5' end has a 2'-O-MOE modification, the sequence before the transition sequence TTTTT is the sequence of the PD-L1 adaptor, and the sequence after the transition sequence TTTTT is the c sequence.

[1098] Drug 91): BCMA aptamer-CD38 aptamer-CpG-BYZD-CD19 aptamer-AmiR-21-DNA vector, wherein the a sequence, b sequence, and c sequence of the DNA vector are as follows:

[1099] The a sequence is: SEQ ID NO: 15: GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC, wherein the underlined portion is the single-stranded connecting bridge sequence A;

[1100] The b sequence is: SEQ ID NO: 16: CCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, wherein the underlined portion is the single-stranded connecting bridge sequence B;

[1101] The c sequence is: SEQ ID NO: 17: GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG, wherein the underlined portion is the single-stranded connecting bridge sequence C;

[1102] The CD38 aptamer is connected to the complementary sequence A' of the single-stranded bridge sequence A via the transition sequence TT and CpG-BYZD. The complementary sequence A' is complementary to the single-stranded bridge sequence A. The CD38 aptamer-CpG-BYZD-complementary sequence A' is:

[1103] SEQ ID NO: 332: TACGTGAATCTCGTACGATACTCTGTAAGCGTTTAGCGAAGCCACCGTGCTACA, wherein SEQ ID NO: 170: TACGTGAATCTCGTACGATACTCTGTAAGCGT is a CD38 aptamer, and the phosphate backbone between the first four nucleotides at the 5' end has a thiolation modification; SEQ ID NO: 8: GCCACCGTGCTACA is a complementary sequence, A'TT is a transition sequence, and AGCGAA is CpG-BYZD;

[1104] The CD19 aptamer is connected to the 5' end of the complementary sequence B' of the single-stranded bridge sequence B via AmiR-21. The complementary sequence B' is complementary to the single-stranded bridge sequence B. The CD19 aptamer-AmiR-21-complementary sequence B' is:

[1105] SEQ ID NO: 333: UGAGCCCCUGUUCGACAGGAGGCUCAGAUAAGCUCACGGCCGCGCCGA, wherein SEQ ID NO: 160: UGAGCCCCUGUUCGACAGGAGGCUCA is the sequence of the CD19 aptamer, wherein the C and U bases have 2'F modifications; GAUAAGCU is the sequence of AmiR-21, wherein the C and U bases have 2'F modifications; SEQ ID NO: 10: CACGGCCGCGCCGA is the complementary sequence B';

[1106] The BCMA aptamer is connected to the 5' end of the complementary sequence C' of the single-stranded bridge sequence C via the transition sequence AA. The complementary sequence C' is complementary to the single-stranded bridge sequence C. The BCMA aptamer-transition sequence AA-complementary sequence C' is:

[1107] SEQ ID NO:334: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUACAACAGCAGCAGCAGCA, wherein SEQ ID NO:12: CAGCAGCAGCAGCA is the complementary sequence C', SEQ ID NO:140: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUAC is the sequence of the BCMA aptamer, and the C and U bases in the RNA sequence of the BCMA aptamer have 2'F modifications.

[1108] Drug 92): BCMA aptamer-CD38 aptamer-CD19 aptamer-AmiR-21-DNA vector, wherein the a sequence, b sequence, and c sequence of the DNA vector are as follows:

[1109] The a sequence is: SEQ ID NO: 15: GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC, wherein the underlined portion is the single-stranded connecting bridge sequence A;

[1110] The b sequence is: SEQ ID NO: 16: CCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, wherein the underlined portion is the single-stranded connecting bridge sequence B;

[1111] The c sequence is: SEQ ID NO: 17: GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG, wherein the underlined portion is the single-stranded connecting bridge sequence C;

[1112] The CD38 aptamer is connected to the complementary sequence A' of the single-stranded bridge sequence A through the transition sequence TTTTT. The complementary sequence A' is complementary to the single-stranded bridge sequence A. The sequence of CD38 aptamer-transition sequence TTTTT-complementary sequence A' is:

[1113] SEQ ID NO: 335: TACGTGAATCTCGTACGATACTCTGTAAGCGTTTTTTGCCACCGTGCTACA, SEQ ID NO: 170: TACGTGAATCTCGTACGATACTCTGTAAGCGT is the sequence of the CD38 aptamer, wherein the phosphate backbone between the first four nucleotides at the 5' end has a thiolation modification; SEQ ID NO: 8: GCCACCGTGCTACA is the complementary sequence A' of the single-stranded connecting bridge sequence A;

[1114] The CD19 aptamer is connected to the complementary sequence B' of the single-stranded bridge sequence B through AmiR-21, and the complementary sequence B' is complementary to the single-stranded bridge sequence B. The sequence of CD19 aptamer-AmiR-21-complementary sequence B' is:

[1115] SEQ ID NO: 333: UGAGCCCCUGUUCGACAGGAGGCUCAGAUAAGCUCACGGCCGCGCCGA, wherein SEQ ID NO: 160: UGAGCCCCUGUUCGACAGGAGGCUCA is the sequence of the CD19 aptamer, wherein C and U have 2'F modifications; GAUAAGCU is the sequence of AmiR-21, wherein C and U have 2'F modifications; SEQ ID NO: 10: CACGGCCGCGCCGA is the complementary sequence B';

[1116] The BCMA aptamer is connected to the 5' end of the complementary sequence C' of the single-stranded bridge sequence C via the transition sequence AA. The complementary sequence C' is complementary to the single-stranded bridge sequence C. The BCMA aptamer-transition sequence AA-complementary sequence C' is:

[1117] SEQ ID NO: 334: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUACAACAGCAGCAGCAGCA, wherein SEQ ID NO: 12: CAGCAGCAGCAGCA is the complementary sequence C'. SEQ ID NO: 140: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUAC is the sequence of the BCMA aptamer, and the C and U bases in the RNA sequence of the BCMA aptamer have 2'F modifications.

[1118] Drug 93): CpG2006-CD38 aptamer-PD-L1 aptamer-DNA vector, wherein the a sequence, b sequence, and c sequence of the DNA vector are as follows:

[1119] The a sequence is: SEQ ID NO: 15: GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC, wherein the underlined portion is the single-stranded connecting bridge sequence A;

[1120] The b sequence is: SEQ ID NO: 16: CCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, wherein the underlined portion is the single-stranded connecting bridge sequence B;

[1121] The c sequence is: SEQ ID NO: 17: GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG, wherein the underlined portion is the single-stranded connecting bridge sequence C;

[1122] The CD38 aptamer is connected to the complementary sequence A' of the single-stranded bridge sequence A through the transition sequence TTTTT. The complementary sequence A' is complementary to the single-stranded bridge sequence A and connected to the 3' end of the a sequence. The sequence of CD38 aptamer-transition sequence TTTTT-complementary sequence A' is:

[1123] SEQ ID NO: 335: TACGTGAATCTCGTACGATACTCTGTAAGCGTTTTTTGCCACCGTGCTACA, SEQ ID NO: 170: TACGTGAATCTCGTACGATACTCTGTAAGCGT is the sequence of the CD38 aptamer, wherein the phosphate backbone between the first four nucleotides at the 5' end has a thiolation modification; SEQ ID NO: 8: GCCACCGTGCTACA is the complementary sequence A' of the single-stranded connecting bridge sequence A;

[1124] The PD-L1 aptamer is connected to the 5' end of the complementary sequence B' of the single-stranded bridge sequence B through the transition sequence TTTTT. The PD-L1 aptamer is connected to the 3' end of the b sequence through the complementary pairing of the complementary sequence B' and the single-stranded bridge sequence B.

[1125] CpG2006 is connected to the 5' end of the complementary sequence C' of the single-stranded bridge C sequence through the transition sequence TTTTT, and CpG2006 is connected to the 3' end of the c sequence through the complementary pairing between the complementary sequence C' and the single-stranded bridge C sequence;

[1126] The sequence of the PD-L1 aptamer-transition sequence TTTTT-complementary sequence B' is: SEQ ID NO: 336: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGTTTTTTCACGGCCGCGCCGA, wherein the phosphate backbone between the first four adjacent nucleotides at the 5' end is thiolated; wherein, SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT is the sequence of the PD-L1 aptamer, and SEQ ID NO: 10: CACGGCCGCGCCGA is the complementary sequence B';

[1127] The sequence of CpG2006-transition sequence TTTTT-complementary sequence C' is:

[1128] SEQ ID NO:337:TCGTCGTTTTGTCGTTTTGTCGTTTTTTTCAGCAGCAGCAGCA, wherein SEQ ID NO:57:TCGTCGTTTTGTCGTTTTGTCGTT is the sequence of CpG2006, in which the phosphate backbone between adjacent nucleotides has a thio modification; SEQ ID NO:12:CAGCAGCAGCAGCA is the complementary sequence C'.

[1129] Drug 94): BCMA aptamer-CD38 aptamer-CpG-BYZD-PD-L1 aptamer-DNA vector, wherein the a sequence, b sequence, and c sequence of the DNA vector are as follows:

[1130] The a sequence is: SEQ ID NO: 15: GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC, wherein the underlined portion is the single-stranded connecting bridge sequence A;

[1131] The b sequence is: SEQ ID NO: 16: CCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, wherein the underlined portion is the single-stranded connecting bridge sequence B;

[1132] The c sequence is: SEQ ID NO: 17: GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG, wherein the underlined portion is the single-stranded connecting bridge sequence C;

[1133] The CD38 aptamer is connected to the complementary sequence A' of the single-stranded bridge sequence A through CpG-BYZD. The complementary sequence A' is complementary to the single-stranded bridge sequence A and connected to the 3' end of the a sequence. The sequence of CD38 aptamer-CpG-BYZD-complementary sequence A' is:

[1134] SEQ ID NO: 332: TACGTGAATCTCGTACGATACTCTGTAAGCGTTTAGCGAAGCCACCGTGCTACA, SEQ ID NO: 170: TACGTGAATCTCGTACGATACTCTGTAAGCGT is the sequence of the CD38 aptamer, wherein the phosphate backbone between the first four nucleotides at the 5' end has a thiolation modification; SEQ ID NO: 8: GCCACCGTGCTACA is the complementary sequence A' of the single-stranded connecting bridge sequence A; TT is a transition sequence, and AGCGAA is CpG-BYZD;

[1135] The PD-L1 aptamer is connected to the 5' end of the complementary sequence B' of the single-stranded bridge sequence B through the transition sequence TTTTT. The PD-L1 aptamer is connected to the 3' end of the b sequence through the complementary pairing of the complementary sequence B' and the single-stranded bridge sequence B.

[1136] The BCMA aptamer is directly linked to the 5' end of the complementary sequence C' of the single-stranded bridge C sequence, and the BCMA aptamer is linked to the 3' end of the C sequence through complementary pairing between the complementary sequence C' and the single-stranded bridge C sequence;

[1137] The sequence of the PD-L1 aptamer-transition sequence TTTTT-complementary sequence B' is: SEQ ID NO: 336: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGTTTTTTCACGGCCGCGCCGA, wherein the phosphate backbone between the first four adjacent nucleotides at the 5' end is thiolated; wherein, SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT is the sequence of the PD-L1 aptamer, and SEQ ID NO: 10: CACGGCCGCGCCGA is the complementary sequence B';

[1138] The sequence of BCMA aptamer-transition sequence AA-complementary sequence C' is:

[1139] SEQ ID NO: 334: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUACAACAGCAGCAGCAGCA, wherein SEQ ID NO: 140: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUAC is a BCMA aptamer, and the C and U bases in the RNA sequence of the BCMA aptamer have 2'F modifications; SEQ ID NO: 12: CAGCAGCAGCAGCA is the complementary sequence C'.

[1140] Drug 95): BCMA aptamer-CD40 aptamer-PD-L1 aptamer-DNA vector, wherein the a sequence, b sequence, and c sequence of the DNA vector are as follows:

[1141] The a sequence is: SEQ ID NO: 15: GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC, wherein the underlined portion is the single-stranded connecting bridge sequence A;

[1142] The b sequence is: SEQ ID NO: 16: CCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, wherein the underlined portion is the single-stranded connecting bridge sequence B;

[1143] The c sequence is: SEQ ID NO: 17: GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG, wherein the underlined portion is the single-stranded connecting bridge sequence C;

[1144] The CD40 aptamer is connected to the complementary sequence A' of the single-stranded bridge sequence A through the transition sequence TTTTT. The complementary sequence A' is complementary to the single-stranded bridge sequence A and connected to the 3' end of the a sequence. The sequence of CD40 aptamer-transition sequence TTTTT-complementary sequence A' is:

[1145] SEQ ID NO: 338: GCCAACGAGTAGGCGATAGCGCGTGGCTTTTTGCCACCGTGCTACA, wherein SEQ ID NO: 156: GCCAACGAGTAGGCGATAGCGCGTGGC is a CD40 aptamer, and the phosphate backbone between the first four nucleotides at the 5' end has a thiolation modification; SEQ ID NO: 8: GCCACCGTGCTACA is the complementary sequence A'

[1146] The PD-L1 aptamer is connected to the 5' end of the complementary sequence B' of the single-stranded bridge sequence B through the transition sequence TTTTT. The PD-L1 aptamer is connected to the 3' end of the b sequence through the complementary pairing of the complementary sequence B' and the single-stranded bridge sequence B.

[1147] The BCMA aptamer is directly linked to the 5' end of the complementary sequence C' of the single-stranded bridge C sequence, and the BCMA aptamer is linked to the 3' end of the C sequence through complementary pairing between the complementary sequence C' and the single-stranded bridge C sequence;

[1148] The sequence of the PD-L1 aptamer-transition sequence TTTTT-complementary sequence B' is: SEQ ID NO: 336: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGTTTTTTCACGGCCGCGCCGA, wherein the phosphate backbone between the first four adjacent nucleotides at the 5' end is thiolated; wherein, SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT is the sequence of the PD-L1 aptamer, and SEQ ID NO: 10: CACGGCCGCGCCGA is the complementary sequence B';

[1149] The sequence of BCMA aptamer-transition sequence AA-complementary sequence C' is:

[1150] SEQ ID NO: 334: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUACAACAGCAGCAGCAGCA, wherein SEQ ID NO: 140: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUAC is a BCMA aptamer, and the C and U bases in the RNA sequence of the BCMA aptamer have 2'F modifications; SEQ ID NO: 12: CAGCAGCAGCAGCA is the complementary sequence C'.

[1151] Drug 96): AmiR-21-AS1411 aptamer-CD40 aptamer-2*biotin-DNA vector, wherein the DNA vector is group 1) of the aforementioned 26 backbone sequence nucleic acid vectors, AmiR-21 is linked to the 5' end of sequence a, the AS1411 aptamer is linked to the 5' end of sequence b via the transition sequence TTTTT, and the CD40 aptamer is linked to the 5' end of sequence c via the transition sequence TTTTT, one biotin is modified at the 3' end of sequence a, and another biotin is modified at the 3' end of sequence c;

[1152] The sequence of AmiR21 is GATAAGCT, with each nucleotide having a locked nucleic acid modification;

[1153] The sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG;

[1154] The sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG.

[1155] Drug 97): 2*AmiR-21-4*Biotin-DNA vector;

[1156] Among them, the DNA vector is the 11th group of nucleic acid vectors of the aforementioned 26 backbone sequences, two AmiR21s are directly connected to the 5' end of sequence a and sequence c, respectively, and four biotins are connected to the 3' end of sequence a, the 5' end and 3' end of sequence b, and the 3' end of sequence c, respectively.

[1157] Preferably, the sequence of AmiR-21 is GATAAGCT, wherein each position is a locked nucleic acid modification.

[1158] Drug 98): TTA1 aptamer-epirubicin-4*biotin-DNA vector;

[1159] The DNA vector is the 13th group of nucleic acid vectors among the aforementioned 26 backbone sequences, the four AmiR21s are directly linked to the 5' and 3' ends of sequence a and sequence c, respectively, the TTA1 aptamer is linked to the 5' end of sequence b via a transition sequence, and epirubicin is specifically inserted between adjacent GC base pairs of the nucleic acid vector;

[1160] Preferably, the sequence of the TTA1 aptamer is:

[1161] SEQ ID NO:265: CCTGCACTTGGCTTGGATTTCAGAAGGGAGACCC.

[1162] Drug 99): TTA1 aptamer-2*Survivin siRNA-DNA vector;

[1163] The DNA vector is the 13th group of nucleic acid vectors of the aforementioned 26 backbone sequences, the TTA1 aptamer is connected to the 5' end of the b sequence via a transition sequence, the sense strands of two survivin siRNAs are connected to the 3' ends of the b sequence and the c sequence, and the antisense strands of two survivin siRNAs are connected to the 3' ends of the b sequence and the c sequence via complementary pairing with the sense strands of the survivin siRNAs;

[1164] Preferably, the TTA1 aptamer is:

[1165] SEQ ID NO:265: CCTGCACTTGGCTTGGATTTCAGAAGGGAGACCC;

[1166] Preferably, the antisense strand of Survivin siRNA is: SEQ ID NO: 300: UGUGACAGAUAAGGAACCUGCAG;

[1167] The sense strand of Survivin siRNA is: SEQ ID NO: 100: GCAGGUUCCUUAUCUGUCACAUU; both the sense strand and the antisense strand of Survivin siRNA have thiolation modifications in the phosphate backbone between the first three adjacent nucleotides at the 5' end and between the last three adjacent nucleotides at the 3' end.

[1168] Drug 100): CD16a aptamer-CD40 aptamer-CpG2006-DNA, wherein the DNA vector is the nucleic acid vector of group 6), the CD16a aptamer is linked to the 5' end of sequence a via a transition sequence, the CD40 aptamer is linked to the 3' end of sequence b via a transition sequence, and CpG2006 is linked to the 5' end of sequence c via a transition sequence;

[1169] Preferably, the sequence of the CD16a aptamer is SEQ ID NO: 157:

[1170] CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the 1st to 3rd phosphate backbones at the 5' end are thio-modified;

[1171] Preferably, the sequence of the CD40 aptamer is SEQ ID NO: 154:

[1172] CCAACGAGTAGGCGATAGCGCGTGG, the 1st to 3rd phosphate backbones at the 5' end are thio-modified;

[1173] Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and the phosphate backbones between adjacent nucleotides are all thio-modified;

[1174] Preferably, the transition sequence is TTTTT.

[1175] In a third typical embodiment of the present application, a pharmaceutical composition is provided, comprising any one or more of the above-mentioned nucleic acid drugs, and optionally a pharmaceutically acceptable carrier and / or excipient.

[1176] Furthermore, at least one drug in the pharmaceutical composition is selected from the nucleic acid drug of claim 12, and the pharmaceutical composition is selected from any one of the following combinations;

[1177] Combination 1): drug 2) + drug 21);

[1178] Combination 2): drug 6) + drug 26);

[1179] Combination 3): drug 6) + OX40 aptamer in RNA form;

[1180] Combination 4): drug 3) + drug 26);

[1181] Combination 5): drug 3) + drug 21) + OX40 aptamer in DNA form;

[1182] Combination 6): drug 4) + drug 21) + DNA-formed OX40 aptamer;

[1183] Combination 7): drug 4) + drug 21);

[1184] Combination 8): drug 3) + drug 23);

[1185] Combination 9): drug 4) + drug 23);

[1186] Combination 10): drug 3) + drug 24) + OX40 aptamer in DNA form;

[1187] Combination 11): drug 3) + drug 41);

[1188] Combination 12): drug 5) + drug 41);

[1189] Combination 13): drug 5) + drug 96);

[1190] Combination 14): drug 96) + drug 41);

[1191] Combination 15): drug 3) + drug 97) + OX40 aptamer in DNA form;

[1192] Combination 16): drug 4) + drug 20) + OX40 aptamer in DNA form;

[1193] Combination 17): drug 4) + drug 20);

[1194] Combination 18): drug 7) + drug 25) + OX40 aptamer in DNA form;

[1195] Combination 19): drug 1) + drug 18) + drug 98);

[1196] Combination 20): drug 1) + drug 18) + DNA form of OX40 aptamer + drug 99);

[1197] Combination 21): drug 3) + drug 18) + OX40 aptamer in DNA form;

[1198] Combination 22): drug 3) + drug 18);

[1199] Combination 23): drug 3) + OX40 aptamer in DNA form;

[1200] Combination 24): drug 3) + drug 18) + OX40 aptamer in locked nucleic acid form;

[1201] Combination 25): drug 3) + drug 18) + OX40 aptamer in RNA form;

[1202] Combination 26): drug 3) + drug 18) + CD40 aptamer in DNA form

[1203] Combination 27): drug 3) + drug 20) + CD40 aptamer in DNA form;

[1204] Combination 28): drug 4) + drug 19) + CD40 aptamer in DNA form;

[1205] The sequence of the DNA-based OX40 aptamer is:

[1206] SEQ ID NO:227:CAGTCTGCATCGTAGGATTAGCCACCGUATCTTTCCCAC;

[1207] The sequence of the RNA form of the OX40 aptamer is:

[1208] SEQ ID NO: 226: GGGAGGACGAUGCGGCAGUCUGCAUCGUAGGAAUCGCCACCGUAUACUUUCCCACCAGACGACUCGCUGAGGAUCCGAGA;

[1209] The locked nucleic acid-form OX40 aptamer has locked nucleic acid modifications at the first five nucleotides at the 5' end and the first four nucleotides at the 3' end in the sequence of the DNA-form OX40 aptamer.

[1210] In a fourth typical embodiment of the present application, a method is provided for preparing a drug for treating tumors, liver diseases other than liver cancer, or diseases caused by coronavirus infection by using any of the aforementioned nucleic acid vectors, nucleic acid drugs, or pharmaceutical compositions.

[1211] Furthermore, liver diseases other than liver cancer are hepatitis B or hepatitis C; diseases caused by coronavirus infection include COVID-19; tumors are male tumors, gynecological tumors, respiratory system tumors, digestive system tumors, hematological tumors, urinary system tumors, bone marrow tumors, neurological tumors, dermatological tumors, general surgery tumors or ENT tumors; preferably, male tumors are prostate cancer, penile cancer, testicular tumors or male urethra cancer, gynecological tumors are ovarian cancer, cervical cancer, endometrial cancer, uterine fibroids, vulvar cancer or malignant hydatidiform mole, respiratory system tumors are lung cancer, non-small cell lung cancer, small cell lung cancer, nasopharyngeal cancer, tracheal tumors, lung cancer metastasis, pneumonia The following types of cancers are classified into: pulmonary pseudotumor or radiation-induced lung cancer; digestive system tumors include liver cancer, stomach cancer, colorectal cancer, gallbladder cancer, esophageal cancer, rectal cancer, pancreatic cancer or colon cancer; hematological tumors include leukemia, lymphoma, lymphosarcoma or multiple myeloma, kidney cancer, bladder cancer or urinary cancer; bone marrow tumors include giant cell tumor of bone, osteochondroma or osteosarcoma; neurological tumors include brain tumor, meningioma, brain tuberculoma, pituitary tumor, neuroblastoma, glioblastoma or brain glioma; dermatological tumors include skin cancer or melanoma; general surgical tumors include breast cancer, lipoma, thyroid cancer or thyroid tumor; ENT tumors include oral cancer, tongue cancer, laryngeal cancer, middle ear cancer, gingival cancer or orbital tumor.

[1212] Furthermore, during the application process, the drug is administered by tumor administration, intravenous administration or intraperitoneal administration.

[1213] Furthermore, the daily dosage of the drug during application is 0.1 μg / Kg to 100 mg / Kg.

[1214] In a fifth typical embodiment of the present application, a method for preparing any of the aforementioned nucleic acid drugs is provided, the preparation method comprising obtaining a nucleic acid drug by self-assembly of at least one chain from a nucleic acid vector containing sequence a, sequence b, and sequence c and at least one oligonucleotide effector molecule mounted on the nucleic acid vector; wherein the oligonucleotide effector molecule is selected from at least one of the following: a nucleic acid immunostimulant, a nucleic acid aptamer, siRNA, miRNA, and an ASO.

[1215] Furthermore, the nucleic acid drug is obtained by self-assembly of 2-8, preferably 3-6 chains.

[1216] Furthermore, when self-assembly is performed by more than 3 chains, the preparation method includes: providing the following three modified or unmodified sequences for self-assembly to form a nucleic acid vector: sequence a, sequence b and sequence c, where modification refers to modification with a chemical small molecule with a targeting effect; and attaching the sequence of at least one oligonucleotide effector molecule to the 5' end and / or 3' end of at least one of the sequences a, b and c of the nucleic acid vector by sequence complementarity; wherein the oligonucleotide effector molecule is selected from at least one of the following: nucleic acid immunostimulants, nucleic acid aptamers, siRNA, miRNA and ASO.

[1217] Furthermore, when the oligonucleotide effector molecule includes siRNA, the sense chain of the siRNA is synthesized at the 5' end and / or 3' end of at least one of the modified or unmodified a sequence, b sequence and c sequence, and the antisense chain of the siRNA is self-assembled with the modified or unmodified a sequence, b sequence and c sequence, thereby connecting the siRNA to the nucleic acid vector through complementary pairing of the antisense chain of the siRNA and the sense chain of the siRNA; preferably, the sense chain of the siRNA is directly synthesized at the 5' end and / or 3' end of at least one of the a sequence, b sequence and c sequence through a transition sequence; preferably, the transition sequence is selected from 2 to 8, preferably 3-6 consecutive T, A or U.

[1218] Furthermore, the oligonucleotide effector molecule includes miRNA and / or a nucleic acid immunostimulator, and the miRNA is directly synthesized and / or the nucleic acid immunostimulator is synthesized through a transition sequence at the 5' end and / or 3' end of at least one of the modified or unmodified a sequence, b sequence and c sequence, and the miRNA and / or nucleic acid immunostimulator is mounted on the nucleic acid carrier through self-assembly of the modified or unmodified a sequence, b sequence and c sequence; preferably, the transition sequence is selected from 2 to 8, preferably 3-6 consecutive T or A.

[1219] Furthermore, the oligonucleotide effector molecule includes a nucleic acid aptamer, which is synthesized at the 5' end and / or 3' end of at least one of the modified or unmodified a sequence, b sequence and c sequence, and the nucleic acid aptamer is mounted on the nucleic acid carrier through self-assembly of the modified or unmodified a sequence, b sequence and c sequence; preferably, the nucleic acid aptamer is directly synthesized at the 5' end and / or 3' end of at least one of the a sequence, b sequence and c sequence through a transition sequence; preferably, the transition sequence is selected from 2 to 8, preferably 3-6 consecutive T or A.

[1220] Furthermore, when the oligonucleotide effector molecule further includes a nucleic acid immunostimulator and / or a nucleic acid aptamer on the basis of including siRNA, the nucleic acid immunostimulator is synthesized through a transition sequence at the 5' end and / or 3' end of at least one of the modified or unmodified a sequence, b sequence and c sequence, and is different from the end of the siRNA sense chain, and / or the nucleic acid aptamer is synthesized through a transition sequence at the 5' end of the antisense chain of the siRNA to obtain an aptamer-siRNA fragment; the aptamer-siRNA fragment is co-incubated with the modified or unmodified a sequence, b sequence and c sequence synthesized with the nucleic acid immunostimulator for self-assembly, thereby mounting the nucleic acid aptamer on the nucleic acid carrier through the complementarity between the antisense chain of the siRNA and the sense chain of the siRNA.

[1221] Furthermore, when the oligonucleotide effector molecule includes miRNA and nucleic acid aptamer, the nucleic acid aptamer is synthesized at the 5' end or 3' end of the miRNA to obtain a nucleic acid aptamer-miRNA fusion single-stranded sequence; the nucleic acid aptamer-miRNA fusion single-stranded sequence is allowed to participate in self-assembly, thereby mounting the nucleic acid aptamer and miRNA on a nucleic acid carrier.

[1222] Furthermore, when the oligonucleotide effector molecule includes a nucleic acid immunostimulator and a nucleic acid aptamer, the nucleic acid immunostimulator and the nucleic acid aptamer are independently synthesized at any end of at least one of the modified or unmodified a sequence, b sequence and c sequence to obtain a nucleic acid immunostimulator and / or nucleic acid aptamer fusion sequence, so that the nucleic acid immunostimulator and / or nucleic acid aptamer fusion sequence participate in self-assembly, thereby mounting the nucleic acid aptamer and nucleic acid immunostimulator on a nucleic acid carrier.

[1223] Furthermore, sequence a, sequence b, and sequence c respectively include a carrier backbone sequence and a single-stranded bonding bridge sequence, and one or more oligonucleotide effector molecules self-assemble with sequence a, sequence b, and sequence c through the complementary sequence of the single-stranded bonding bridge sequence to form a nucleic acid drug; preferably, sequence a, sequence b, and sequence c are as follows:

[1224] The a sequence is: SEQ ID NO: 15: GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC, wherein the underlined portion is the single-stranded connecting bridge sequence A;

[1225] The b sequence is: SEQ ID NO: 16: CCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, wherein the underlined portion is the single-stranded connecting bridge sequence B;

[1226] The c sequence is: SEQ ID NO: 17: GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG, wherein the underlined portion is the single-stranded connecting bridge sequence C.

[1227] Furthermore, the nucleic acid drug is a CpG2006-CD40 aptamer-PD-L1 aptamer-DNA vector, and the preparation method includes any one of the following self-assembly methods;

[1228] 1) Three chains self-assemble, where the three chains are:

[1229] CpG2006-a sequence:

[1230] SEQ ID NO: 309: TCGTCGTTTTGTCGTTTTGTCGTTTTTTTGCGACGCCCACGAGCGTTCCGGGAGAGGAGC, the phosphate backbone between adjacent nucleotides 1-24 before the 5' end has a thiolation modification, TTTTT is a transition sequence, the sequence before TTTTT is CpG2006, and the sequence after TTTTT is an a sequence;

[1231] CD40 aptamer-b sequence:

[1232] SEQ ID NO: 330: CCAACGAGTAGGCGATAGCGCGTGGTTTTTGCTCCTCTCCCGGTTCGCCGCGAGCCGCG, the phosphate backbone between the first 1-5 adjacent nucleotides at the 5' end has a thiolation modification, TTTTT is a transition sequence, the sequence before TTTTT is the CD40 aptamer sequence, and the sequence after TTTTT is the b sequence; and

[1233] PD-L1 aptamer-c sequence:

[1234] SEQ ID NO: 331: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGTTTTTTCGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the phosphate backbone between the first 1-5 adjacent nucleotides at the 5' end has a thiolation modification, TTTTT is a transition sequence, the sequence before TTTTT is the PD-L1 aptamer sequence, and the sequence after TTTTT is the c sequence;

[1235] 2) 4 chains self-assemble, where the 4 chains are:

[1236] CpG2006-a sequence:

[1237] SEQ ID NO: 309: TCGTCGTTTTGTCGTTTTGTCGTTTTTTTGCGACGCCCACGAGCGTTCCGGGAGAGGAGC, the phosphate backbone between adjacent nucleotides 1-24 before the 5' end has a thiolation modification, TTTTT is a transition sequence, the sequence before TTTTT is CpG2006, and the sequence after TTTTT is an a sequence;

[1238] CD40 aptamer-b sequence:

[1239] SEQ ID NO: 339: CCAACGAGTAGGCGATAGCGCGTGGTTTGCTCCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, the phosphate backbone between the first 1-4 adjacent nucleotides at the 5' end has a thiolation modification, TTT is a transition sequence, the sequence before TTT is the CD40 aptamer sequence, and the sequence after TTT is the b sequence;

[1240] PD-L1 aptamer-transition sequence-complementary sequence B' of single-stranded bridge sequence B:

[1241] SEQ ID NO: 336: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGTTTTTTCACGGCCGCGCCGA, the phosphate backbone between the first 1-4 adjacent nucleotides at the 5' end has a thiolation modification, TTTTT is a transition sequence, the sequence before TTTTT is the PD-L1 aptamer sequence, and the sequence after TTTTT is the complementary sequence B'; and

[1242] c-sequence:

[1243] SEQ ID NO: 340: GGCTCGCGGCCATAGCCGTGGGCGTCGC;

[1244] or

[1245] The 4 chains are:

[1246] CpG2006--transition sequence-complementary sequence C' of single-stranded bridge sequence C:

[1247] SEQ ID NO: 341: TCGTCGTTTTGTCGTTTTGTCGTTTTTTTTCAGCAGCAGCAGCA, the phosphate backbone between adjacent nucleotides 1-24 before the 5' end has a thiolation modification, TTTTT is a transition sequence, the sequence before TTTTT is CpG2006, and the sequence after TTTTT is a complementary sequence C';

[1248] a Sequence: SEQ ID NO: 18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC;

[1249] CD40 aptamer-b sequence:

[1250] SEQ ID NO: 339: CCAACGAGTAGGCGATAGCGCGTGGTTTGCTCCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, the phosphate backbone between the first 1-4 adjacent nucleotides at the 5' end has a thiolation modification, TTT is a transition sequence, the sequence before TTT is the CD40 aptamer sequence, and the sequence after TTT is the b sequence;

[1251] PD-L1 aptamer-c sequence:

[1252] SEQ ID NO: 342: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGTTTTTTGGCTCGCGGCCATAGCCGTGGGCGTCGC, the phosphate backbone between the first 1-4 adjacent nucleotides at the 5' end has a thiolation modification, TTTTT is a transition sequence, the sequence before TTTTT is the PD-L1 aptamer sequence, and the sequence after TTTTT is the c sequence;

[1253] 3) 5 chains self-assemble, where the 5 chains are:

[1254] a Sequence: SEQ ID NO: 15: GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC;

[1255] CD40 aptamer-transition sequence-b sequence:

[1256] SEQ ID NO: 339: CCAACGAGTAGGCGATAGCGCGTGGTTTGCTCCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, the phosphate backbone between the first 1-4 adjacent nucleotides at the 5' end has a thiolation modification, TTT is a transition sequence, the sequence before TTT is the CD40 aptamer sequence, and the sequence after TTT is the b sequence;

[1257] PD-L1 aptamer-transition sequence-complementary sequence B' of single-stranded bridge sequence B:

[1258] SEQ ID NO: 336: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGTTTTTTCACGGCCGCGCCGA, the phosphate backbone between the first 1-4 adjacent nucleotides at the 5' end has a thiolation modification, TTTTT is a transition sequence, the sequence before TTTTT is the PD-L1 aptamer sequence, and the sequence after TTTTT is the complementary sequence B';

[1259] CpG2006 sequence-transition sequence-single-stranded bridge sequence C' complementary sequence:

[1260] SEQ ID NO: 337: TCGTCGTTTTGTCGTTTTGTCGTTTTTTTCAGCAGCAGCAGCA, the phosphate backbone between adjacent nucleotides 1-24 before the 5' end has a thiolation modification, TTTTT is a transition sequence, the sequence before TTTTT is CpG2006, and the sequence after TTTTT is a complementary sequence C';

[1261] c sequence: SEQ ID NO: 17: GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG;

[1262] Or the 5 chains are:

[1263] CpG2006-transition sequence-a sequence:

[1264] SEQ ID NO: 343: TCGTCGTTTTGTCGTTTTGTCGTTTTTTTGACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC, the phosphate backbone between adjacent nucleotides 1-24 before the 5' end has a thiolation modification, TTTTT is a transition sequence, the sequence before TTTTT is CpG2006, and the sequence after TTTTT is an a sequence;

[1265] CD40 aptamer-transition sequence-single-stranded bridge sequence A' complementary sequence:

[1266] SEQ ID NO: 338: GCCAACGAGTAGGCGATAGCGCGTGGCTTTTTGCCACCGTGCTACA, the phosphate backbone between the first 1-4 adjacent nucleotides at the 5' end has a thiolation modification, TTTTT is a transition sequence, the sequence before TTTTT is the CD40 aptamer sequence, and the sequence after TTTTT is the complementary sequence A';

[1267] b Sequence: SEQ ID NO: 16: CCTTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG;

[1268] PD-L1 aptamer-transition sequence-complementary sequence B' of single-stranded bridge sequence B:

[1269] SEQ ID NO: 336: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGTTTTTTCACGGCCGCGCCGA, the phosphate backbone between the first 1-4 adjacent nucleotides at the 5' end has a thiolation modification, TTTTT is a transition sequence, the sequence before TTTTT is the PD-L1 aptamer sequence, and the sequence after TTTTT is the complementary sequence B';

[1270] c sequence: SEQ ID NO: 340: GGCTCGCGGCCATAGCCGTGGGCGTCGC;

[1271] 4) 6 chains self-assemble, where the 6 chains are:

[1272] a Sequence: SEQ ID NO: 15: GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC;

[1273] b Sequence: SEQ ID NO: 16: CCTTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG;

[1274] c sequence: SEQ ID NO: 17: GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG;

[1275] CpG2006-transition sequence-single-stranded bridge sequence C' complementary sequence:

[1276] SEQ ID NO: 337: TCGTCGTTTTGTCGTTTTGTCGTTTTTTTCAGCAGCAGCAGCA; the phosphate backbone between adjacent nucleotides 1-24 before the 5' end has a thiolation modification, TTTTT is a transition sequence, the sequence before TTTTT is CpG2006, and the sequence after TTTTT is a complementary sequence C';

[1277] The complementary sequence A' of CD40 aptamer-transition sequence-single-stranded bridge sequence A: SEQ ID NO: 338: GCCAACGAGTAGGCGATAGCGCGTGGCTTTTTGCCACCGTGCTACA, with a thiolation modification on the phosphate backbone between the first 1-4 adjacent nucleotides at the 5' end, TTTTT is the transition sequence, the sequence before TTTTT is the CD40 aptamer sequence, and the sequence after TTTTT is the complementary sequence A';

[1278] PD-L1 aptamer-transition sequence-complementary sequence B' of single-stranded bridge sequence B:

[1279] SEQ ID NO: 336: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGTTTTTTCACGGCCGCGCCGA, the phosphate backbone between the 1-4 adjacent nucleotides before the 5' end has a thio modification, TTTTT is a transition sequence, the sequence before TTTTT is the PD-L1 aptamer sequence, and the sequence after TTTTT is the complementary sequence B'.

[1280] Furthermore, the self-assembly step comprises: dissolving a modified or unmodified sequence a, sequence b, sequence c and an optional sequence of a separately synthesized oligonucleotide effector molecule carrying at least one oligonucleotide effector molecule in an assembly solution, and sequentially performing a denaturation reaction and a renaturation reaction to form a self-assembly crude product; purifying, eluting and evaporating the self-assembly crude product in sequence to obtain a targeted nucleic acid vector carrying at least one oligonucleotide effector molecule; preferably, the molar ratio of sequence a, sequence b and sequence c is 0.90-1.10:0.90-1.10:0.90-1.10, more preferably 1:1:1; preferably, the assembly solution is a TMS aqueous solution, a sodium chloride aqueous solution, a magnesium chloride aqueous solution or purified water; preferably, the temperature of the denaturation reaction is 80-99°C, more preferably 85-9 9°C, further preselected as 90-99°C; preferably, after the denaturation reaction is completed, the reaction system is cooled to the annealing temperature for annealing reaction, and finally cooled to obtain a self-assembled crude product; wherein the insulation temperature is 70-50°C, more preferably 65-55°C, and further preferably 63-57°C; the annealing reaction time is 3-15min, more preferably 3-10min, and further preferably 3-5min; preferably, in the process of cooling the reaction system to the insulation temperature, the cooling rate is 2-10°C / min, more preferably 2-6°C / min, and further preferably 2-3°C / min; preferably, the cooling end temperature is 0-25°C, more preferably 0-15°C, and further preferably 0-4°C; preferably, the pH value of the denaturation reaction is 5.4-8.8.

[1281] The technical solution of this application uses nucleic acid nanoparticles self-assembled from the core sequence listed in this application as delivery vectors for oligonucleotide drugs. Compared with LNPs and PNPs in the prior art, since both the vector itself and the delivered drug are nucleotide sequences, they are more compatible with oligonucleotide drugs in terms of physical and chemical properties. They are convenient for mounting different types of small nucleic acid molecules based on the vector sequence structure or its length, and take advantage of the binding advantages of base complementary pairing, which not only improves delivery efficiency but also makes the delivery system more stable. In addition, the preparation process of nucleic acid vectors is also simpler and more efficient. BRIEF DESCRIPTION OF THE DRAWINGS

[1282] The accompanying drawings, which constitute part of this application, are intended to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are intended to explain the present invention and do not constitute an undue limitation of the present invention. In the accompanying drawings:

[1283] Figures 1-1 to 1-4 show the HPLC chromatograms of the sequence assembly products in Example 1, wherein Figure 1-1 is the HPLC chromatogram of C1, Figure 1-2 is the HPLC chromatogram of C2, Figure 1-3 is the HPLC chromatogram of D1, and Figure 1-4 is the HPLC chromatogram of D2;

[1284] FIG2 shows an agarose gel electrophoresis detection diagram of the self-assembly product of the 3*CPG2006-DNA vector in Example 2;

[1285] FIG3 shows an agarose gel electrophoresis detection image of the self-assembly product of the 2*CpG1826-2*mannose-DNA vector in Example 3;

[1286] FIG4 shows an agarose gel electrophoresis detection image of the 2*CpG1826-CD40 aptamer-DNA vector self-assembly product in Example 4;

[1287] Figure 5-1 shows the agarose gel electrophoresis detection of the 2*CpG2006-CD40 aptamer-DNA vector self-assembly product in Example 5;

[1288] Figure 5-2 shows the HPLC chromatogram of the 2*CpG2006-CD40 aptamer-DNA vector self-assembly product in Example 5;

[1289] Figure 5-3 shows the melting peak and melting curve of the 2*CpG2006-CD40 aptamer-DNA vector in Example 5;

[1290] Figure 5-4 shows an agarose gel electrophoresis detection diagram of the serum stability test of the 2*CpG2006-CD40 aptamer-DNA vector in Example 5;

[1291] FIG6 shows an agarose gel electrophoresis detection image of the 4*CpG2006-CD40 aptamer-DNA vector self-assembly product in Example 6;

[1292] FIG7 shows an agarose gel electrophoresis detection image of the self-assembly product of 2*CpG1826-CD40 aptamer-2*mannose-DNA vector in Example 7;

[1293] FIG8 shows an agarose gel electrophoresis detection image of the self-assembly product of CPG1826-CD40 aptamer-mannose-MUC1 aptamer-DNA vector in Example 8;

[1294] FIG9 shows an agarose gel electrophoresis detection image of the self-assembly product of 2*CpG2006-CD40 aptamer-AmiR-21-3*mannose-DNA vector in Example 9;

[1295] FIG10 shows an agarose gel electrophoresis detection image of the self-assembly product of 2*CPG2006-CD40 aptamer-CD16a aptamer-CTLA-4 aptamer-DNA vector in Example 10;

[1296] FIG11 shows an agarose gel electrophoresis detection image of the 2*CPG2006-CTLA-4 aptamer-PD-L1 aptamer-DNA self-assembly product in Example 11;

[1297] Figure 12-1 shows the agarose gel electrophoresis detection of CCPD3 self-assembly products in Example 12;

[1298] Figure 12-2 shows the HPLC chromatogram of the CCPD3 self-assembly product in Example 12;

[1299] Figure 12-3 shows the melting peak and dissolution curve of the CCPD3 self-assembly product in Example 12;

[1300] Figure 13-1 shows the agarose gel electrophoresis detection of the self-assembled product of CCPD3 variant 1 in Example 13;

[1301] Figure 13-2 shows the HPLC chromatogram of the self-assembled product of CCPD3 variant 1 in Example 13;

[1302] Figure 13-3 shows the agarose gel electrophoresis detection of the self-assembled product of CCPD3 variant 2 in Example 13;

[1303] Figure 13-4 shows the agarose gel electrophoresis detection of the self-assembled product of CCPD3 variant 3 in Example 13;

[1304] Figure 13-5 shows the agarose gel electrophoresis detection of the self-assembled product of CCPD3 variant 4 in Example 13;

[1305] Figure 13-6 shows the agarose gel electrophoresis detection of the self-assembled product of CCPD3 variant 5 in Example 13;

[1306] Figure 13-7 shows the agarose gel electrophoresis detection of the self-assembled product of CCPD3 variant 6 in Example 13;

[1307] Figure 13-8 shows the agarose gel electrophoresis detection of the self-assembled product of CCPD3 variant 7 in Example 13;

[1308] Figure 13-9 shows the agarose gel electrophoresis detection of the self-assembled product of CCPD3 variant 8 in Example 13;

[1309] Figure 13-10 shows the agarose gel electrophoresis detection of the self-assembled product of CCPD3 variant 9 in Example 13;

[1310] Figure 13-11 shows the agarose gel electrophoresis detection of the self-assembled product of CCPD3 variant 10 in Example 13;

[1311] Figures 13-12 show the HPLC chromatogram of the self-assembly product of CCPD3 variant 11 in Example 13;

[1312] Figure 13-13 shows the HPLC chromatogram of the self-assembly product of CCPD3 variant 12 in Example 13;

[1313] Figure 14-1 shows the agarose gel electrophoresis detection of the self-assembly product of 2*CpG2006-CD40-aptamer PD-L1 aptamer-C12 aptamer-DNA vector in Example 14;

[1314] Figure 14-2 shows the agarose gel electrophoresis detection of the 2*AmiR21-TTA1 aptamer-DNA vector self-assembly product in Example 14;

[1315] Figure 14-3 shows the agarose gel electrophoresis detection of the self-assembly product of the 2*AmiR-21-3*Bio-DNA vector in Example 14;

[1316] Figure 14-4 shows the agarose gel electrophoresis detection of the self-assembly product of the 2*AmiR-21-4*Bio-DNA vector in Example 14;

[1317] Figure 14-5 shows the agarose gel electrophoresis detection of the 2*AmiR-21-AS1411 aptamer-DNA vector self-assembly product in Example 14;

[1318] Figure 14-6 shows the agarose gel electrophoresis detection of the self-assembly product of the 2*AmiR-21-AS1411 aptamer-DNA vector enhanced version in Example 14;

[1319] Figure 14-7 shows the agarose gel electrophoresis detection of the 2*AmiR-21-AS1411 aptamer-Bio-DNA vector self-assembly product in Example 14;

[1320] Figure 14-8 shows the agarose gel electrophoresis detection of the 2*AmiR-21-CD40 aptamer-DNA vector self-assembly product in Example 14;

[1321] Figure 14-9 shows the agarose gel electrophoresis detection of the 2*AmiR-21-MUC1 aptamer-3*Bio-DNA vector self-assembly product in Example 14;

[1322] Figure 14-10 shows the agarose gel electrophoresis detection of the self-assembly product of the 2*mannose-2*AmiR-21-DNA vector in Example 14;

[1323] Figure 14-11 shows the agarose gel electrophoresis detection of the self-assembly product of 2*mannose-A15 aptamer-2*AmiR-21-DNA vector in Example 14;

[1324] Figure 14-12 shows the agarose gel electrophoresis detection of the self-assembled product of the 2*mannose-survivin siRNA-DNA vector in Example 14;

[1325] Figure 14-13 shows the agarose gel electrophoresis detection of the self-assembly product of 2*mannose-A15 aptamer-survivin siRNA-AmiR-21-DNA vector in Example 14;

[1326] Figure 14-14 shows the agarose gel electrophoresis detection of the self-assembly product of AS1411 aptamer-Survivin siRNA-PSMA aptamer-3*AmiR-21-RNA vector in Example 14;

[1327] Figures 14-15A show agarose gel electrophoresis detection images of the 3*AmiR-21-AS1411 aptamer-FAP aptamer-DNA vector self-assembly product in Example 14, and Figures 14-15B show HPLC chromatogram detection images;

[1328] Figures 14-16 show agarose gel electrophoresis detection images of the 3*AmiR-21-AS1411 aptamer-CD40 aptamer-2*Bio-DNA vector self-assembly product in Example 14;

[1329] Figures 14-17 show agarose gel electrophoresis detection images of the TAP siRNA-3*AmiR-21-2*AS1411-1 aptamer-DNA vector self-assembly product in Example 14;

[1330] Figures 14-18 show agarose gel electrophoresis detection images of the self-assembly product of the CPG1826-CD40 aptamer-AmiR-21-3*Bio-DNA vector in Example 14;

[1331] Figures 14-19 show agarose gel electrophoresis detection images of the self-assembly product of CD16a aptamer-CTLA-4 aptamer-PD-L1 aptamer-DNA vector in Example 14;

[1332] Figures 14-20 show agarose gel electrophoresis detection images of the self-assembly product of CD16a aptamer-Act-12c aptamer-PD-L1 aptamer-DNA vector in Example 14;

[1333] Figure 14-21A shows an agarose gel electrophoresis detection diagram of the CTLA-4 aptamer-PD-L1 aptamer-PD1 aptamer-DNA vector self-assembly product in Example 14, Figure 14-21B shows an HPLC chromatogram detection diagram, Figure 14-21C shows a melting peak and dissolution curve diagram, and Figure 14-21D shows an agarose gel electrophoresis detection diagram of the serum stability experiment.

[1334] Figures 14-22 show agarose gel electrophoresis detection images of the self-assembly product of CD16a aptamer-Act-12c aptamer-MUC1 aptamer (5TR1)-DNA vector in Example 14;

[1335] Figures 14-23 show agarose gel electrophoresis detection images of the self-assembly product of Her3 aptamer-EGFR siRNA-AS1411 aptamer-Survivin siRNA-Her2 aptamer-DNA vector in Example 14;

[1336] Figures 14-24 show agarose gel electrophoresis detection images of the self-assembly product of AS1411 aptamer-TAP siRNA-CD16a aptamer-Act-12c aptamer-DNA vector in Example 14;

[1337] Figures 14-25 show agarose gel electrophoresis detection images of the self-assembly product of CD16a aptamer-AS1411 aptamer-TAP siRNA-OX40 aptamer-Act-12c aptamer-DNA vector in Example 14;

[1338] Figure 14-26A shows an agarose gel electrophoresis detection diagram of the self-assembly product of AS1411-ASAP1 siRNA-VEGF aptamer-SARS-CoV-2-N48 aptamer-RNA vector in Example 14, and Figure 14-26B shows an HPLC chromatogram detection diagram;

[1339] Figures 14-27 show agarose gel electrophoresis detection images of the self-assembly product of CD3-4 aptamer-PD-1 aptamer-BCMA aptamer-DNA vector in Example 14;

[1340] Figures 14-28 show agarose gel electrophoresis detection images of the self-assembly product of CpG2006-CD38 aptamer-miR-126-PD-L1 aptamer-DNA vector in Example 14;

[1341] Figures 14-29 show the agarose gel electrophoresis detection of the self-assembly product of BCMA aptamer-CD38 aptamer-miR-126-PD-L1 aptamer-miR-34-DNA vector (MM) in Example 14;

[1342] Figures 14-30 show the agarose gel electrophoresis detection of the self-assembly product of AS1411 aptamer-FGF2 aptamer-3*AmiR-21-DNA vector in Example 14;

[1343] Figure 14-31 shows the agarose gel electrophoresis detection of the self-assembly product of HBsAg aptamer-CD40 aptamer-PD-L1 aptamer (CCPD3-C chain)-DNA vector (HBV) in Example 14;

[1344] Figures 14-32 show the agarose gel electrophoresis detection of the self-assembly product of HBsAg aptamer-CD40 aptamer-PD-L1 aptamer (HD)-DNA vector (HBV) in Example 14;

[1345] Figures 14-33 show the agarose gel electrophoresis detection of the BCMA aptamer-CD38 aptamer-CPG aptamer-CD19 aptamer-AmiR-21-DNA3-TY (MM) self-assembly product in Example 14;

[1346] Figures 14-34 show agarose gel electrophoresis detection images of the BCMA aptamer-CD38 aptamer-CD19 aptamer-AmiR-21-DNA3-TY (MM) self-assembly product in Example 14;

[1347] Figures 14-35 show agarose gel electrophoresis detection of the CpG2006-CD38 aptamer-PD-L1 aptamer-DNA3-TY (tumor) self-assembly product in Example 14;

[1348] Figures 14-36 show agarose gel electrophoresis detection images of the self-assembly product of the BCMA aptamer-CD38 aptamer-CPG aptamer-PD-L1 aptamer-DNA3-TY (MM) vector in Example 14;

[1349] Figures 14-37 show the agarose gel electrophoresis detection of the BCMA aptamer-CD40 aptamer-PD-L1 aptamer-DNA3-TY (MM) vector self-assembly product in Example 14;

[1350] Figures 14-38 show the agarose gel electrophoresis detection of the self-assembly product of AmiR-21-AS1411 aptamer-CD40 aptamer-2*biotin-DNA vector in Example 14;

[1351] Figure 14-39 shows the agarose gel electrophoresis detection of the self-assembly product of the 2*AmiR-21-4*biotin-DNA vector in Example 14;

[1352] Figures 14-40 show the agarose gel electrophoresis detection of the TTA1 aptamer-epirubicin-4*biotin-DNA vector self-assembly product in Example 14;

[1353] Figure 14-41 shows the agarose gel electrophoresis detection of the self-assembled product of the universal vector DNA3-TY in Example 14;

[1354] Figure 15-1 shows the HPLC chromatogram of the self-assembled product 1 of CCPD3 in Example 15;

[1355] Figure 15-2 shows the HPLC chromatogram of the self-assembled product 2 of CCPD3 in Example 15;

[1356] Figure 15-3 shows the HPLC chromatogram of the self-assembly product 3 of CCPD3 in Example 15;

[1357] Figure 15-4 shows the HPLC chromatogram of the self-assembly product 4 of CCPD3 in Example 15;

[1358] Figure 15-5 shows the melting peak and dissolution curve of the self-assembled product 1 of CCPD3 in Example 15;

[1359] Figure 15-6 shows the melting peak and dissolution curve of the self-assembled product 5 of CCPD3 in Example 15;

[1360] Figure 15-7 shows the melting peak and dissolution curve of the self-assembled product 6 of CCPD3 in Example 15;

[1361] Figure 15-8 shows the melting peak and dissolution curve of the self-assembled product 7 of CCPD3 in Example 15;

[1362] Figure 15-9 shows the melting peak and dissolution curve of the self-assembled product 8 of CCPD3 in Example 15;

[1363] Figure 15-10 shows the melting peak and dissolution curve of the self-assembled product 9 of CCPD3 in Example 15;

[1364] Figure 15-11 shows the melting peak and dissolution curve of the self-assembled product 10 of CCPD3 in Example 15;

[1365] Figure 15-12 shows the melting peak and dissolution curve of the self-assembled product 11 of CCPD3 in Example 15;

[1366] Figures 15-13 show the melting peak and dissolution curve of the self-assembled product 12 of CCPD3 in Example 15;

[1367] Figures 15-14 show the melting peak and dissolution curve of the self-assembled product 13 of CCPD3 in Example 15;

[1368] Figure 16-1 shows a curve of animal body weight changes in Example 16 (intravenous administration);

[1369] Figure 16-2 shows a curve diagram of animal body weight changes in Example 16 (intratumoral injection);

[1370] Figure 16-3 shows a curve diagram of tumor volume changes on the left side in Example 16 (intravenous administration);

[1371] FIG16-4 shows a curve diagram of the relative volume change of the left tumor in Example 16 (intravenous administration);

[1372] Figure 16-5 shows a curve diagram of tumor volume changes on the left side in Example 16 (intratumoral injection);

[1373] Figure 16-6 shows a curve diagram of the relative volume change of the left tumor in Example 16 (intratumoral injection);

[1374] Figure 16-7 shows a curve diagram of tumor volume changes on the right side in Example 16 (intratumoral injection);

[1375] Figure 16-8 shows a curve diagram of the relative volume change of the right tumor in Example 16 (intratumoral injection);

[1376] Figure 16-9 shows a curve diagram of the change in tumor weight on the right side in Example 16 (administration via tail vein injection);

[1377] Figure 16-10 shows a curve diagram of tumor weight changes on the right side in Example 16 (intratumoral injection);

[1378] Figure 17-1 shows a schematic diagram of the animal vaccination and dosing regimen in Example 17;

[1379] Figure 17-2 shows a curve diagram of animal body weight changes in Example 17;

[1380] Figure 17-3 shows the right tumor growth curve in Example 17;

[1381] Figure 17-4 shows the left tumor growth curve in Example 17;

[1382] Figure 17-5 shows a comparison of tumor weights in Example 17;

[1383] Figure 18-1 shows a schematic diagram of the animal vaccination and dosing regimen in Example 18;

[1384] Figure 18-2 shows a curve diagram of animal body weight changes in Example 18;

[1385] Figure 18-3 shows the tumor growth curve on the drug-administered side in Example 18;

[1386] Figure 18-4 shows the tumor growth curve of the non-drug-treated side in Example 18;

[1387] Figure 18-5 shows a comparison of tumor weights on the drug-administered side in Example 18;

[1388] Figure 18-6 shows a comparison of tumor weights on the non-drug-treated side in Example 18;

[1389] Figure 19-1 shows a schematic diagram of the animal vaccination and dosing regimen in Example 19;

[1390] Figure 19-2 shows a curve diagram of animal body weight changes in Example 19;

[1391] Figure 19-3 shows the right tumor growth curve in Example 19;

[1392] Figure 19-4 shows the left tumor growth curve in Example 19;

[1393] Figure 19-5 shows a comparison of right tumor weights in Example 19;

[1394] Figure 19-6 shows a comparison of tumor weights on the left side in Example 19;

[1395] Figure 20-1 shows a curve diagram of animal body weight changes in Example 20;

[1396] Figure 20-2 shows the left tumor growth curve in Example 20;

[1397] Figure 20-3 shows the relative growth curve of the left tumor in Example 20;

[1398] Figure 20-4 shows the right tumor growth curve in Example 20;

[1399] Figure 20-5 shows the relative growth curve of the left tumor in Example 20;

[1400] Figure 20-6 shows a comparison of right tumor weights in Example 20;

[1401] Figure 21-1 shows a curve diagram of animal body weight changes in Example 21;

[1402] Figure 21-2 shows a tumor growth curve in Example 21;

[1403] Figure 21-3 shows a graph of the relative growth of tumors in Example 21;

[1404] Figure 21-4 shows a comparison of tumor weights in Example 21;

[1405] Figure 22-1 shows a schematic diagram of the animal vaccination and dosing regimen in Example 22;

[1406] Figure 22-2 shows a curve diagram of animal body weight changes in Example 22;

[1407] Figure 22-3 shows the tumor growth curve on the drug-administered side in Example 22;

[1408] Figure 22-4 shows the tumor growth curve of the non-drug-treated side in Example 22;

[1409] Figure 23-1 shows a curve diagram of animal body weight changes in Example 23;

[1410] Figure 23-2 shows a tumor growth curve in Example 23;

[1411] Figure 23-3 shows a graph of the relative tumor growth in Example 23;

[1412] Figure 23-4 shows a comparison of tumor weights in Example 23;

[1413] Figure 24-1 shows a curve diagram of animal body weight changes in Example 24;

[1414] Figure 24-2 shows a tumor growth curve in Example 24;

[1415] Figure 24-3 shows a graph of the relative growth of tumors in Example 24;

[1416] Figure 24-4 shows a comparison of tumor weights in Example 24;

[1417] Figure 25-1 shows a curve diagram of animal body weight changes in Example 25;

[1418] Figure 25-2 shows a tumor growth curve in Example 25;

[1419] Figure 25-3 shows a comparison of tumor weights in Example 25;

[1420] Figure 26-1 shows a curve diagram of animal body weight changes in Example 26;

[1421] Figure 26-2 shows a tumor growth curve in Example 26;

[1422] Figure 26-3 shows a comparison of tumor weights in Example 26;

[1423] Figure 27-1 shows a curve diagram of animal body weight changes in Example 27;

[1424] Figure 27-2 shows a tumor growth curve in Example 27;

[1425] Figure 27-3 shows a graph of the relative growth of tumors in Example 27;

[1426] Figure 27-4 shows a comparison of tumor weights in Example 27;

[1427] Figure 28-1 shows a curve diagram of animal body weight changes in Example 28;

[1428] Figure 28-2 shows a tumor growth curve in Example 28;

[1429] Figure 28-3 shows a graph of the relative growth of tumors in Example 28;

[1430] Figure 28-4 shows a comparison of tumor weights in Example 28;

[1431] Figure 29-1 shows a tumor growth curve in Example 29;

[1432] Figure 29-2 shows a graph of the relative growth of tumors in Example 29;

[1433] Figure 29-3 shows a graph of survival days in Example 29;

[1434] Figure 30-1 shows a curve diagram of animal body weight changes in Example 30;

[1435] Figure 30-2 shows a tumor growth curve in Example 30;

[1436] Figure 30-3 shows a graph of the relative growth of tumors in Example 30;

[1437] Figure 30-4 shows a comparison of tumor weights in Example 30;

[1438] Figure 31-1 shows a curve diagram of animal body weight changes in Example 31;

[1439] Figure 31-2 shows a tumor growth curve in Example 31;

[1440] Figure 31-3 shows a graph of the relative growth of tumors in Example 31;

[1441] Figure 31-4 shows a comparison of tumor weights in Example 31;

[1442] Figure 32-1 shows a curve diagram of animal body weight changes in Example 32;

[1443] Figure 32-2 shows a tumor growth curve in Example 32;

[1444] Figure 32-3 shows a comparison of tumor weights in Example 32;

[1445] Figure 33-1 shows a curve diagram of animal body weight changes in Example 33;

[1446] Figure 33-2 shows a tumor growth curve in Example 33;

[1447] Figure 33-3 shows a comparison of tumor weights in Example 33;

[1448] Figure 34-1 shows a curve diagram of animal body weight changes in Example 34;

[1449] Figure 34-2 shows a tumor growth curve in Example 34;

[1450] Figure 34-3 shows a comparison of tumor weights in Example 34;

[1451] Figure 35-1 shows a curve diagram of animal body weight changes in Example 35;

[1452] Figure 35-2 shows a tumor growth curve in Example 35;

[1453] Figure 35-3 shows a comparison of tumor weights in Example 35;

[1454] Figure 36-1 shows a curve diagram of animal body weight changes in Example 36;

[1455] Figure 36-2 shows a tumor growth curve in Example 36;

[1456] Figure 36-3 shows a comparison of tumor weights in Example 36;

[1457] Figure 37-1 shows a curve diagram of animal body weight changes in Example 37;

[1458] Figure 37-2 shows a tumor growth curve in Example 37;

[1459] Figure 37-3 shows a comparison of tumor weights in Example 37;

[1460] Figure 38-1 shows a curve diagram of animal body weight changes in Example 38;

[1461] Figure 38-2 shows a tumor growth curve in Example 38;

[1462] Figure 38-3 shows a comparison of tumor weights in Example 38;

[1463] Figure 39-1 shows a curve diagram of animal body weight changes in Example 39;

[1464] Figure 39-2 shows a tumor growth curve in Example 39;

[1465] Figure 39-3 shows a comparison of tumor weights in Example 39;

[1466] Figure 40-1 shows a curve diagram of animal body weight changes in Example 40;

[1467] Figure 40-2 shows a tumor growth curve in Example 40;

[1468] Figure 40-3 shows a comparison of tumor weights in Example 40;

[1469] Figure 41-1 shows a schematic diagram of the animal vaccination and dosing regimen in Example 41;

[1470] Figure 41-2 shows a curve diagram of animal body weight changes in Example 41;

[1471] Figure 41-3 shows a tumor growth curve in Example 41;

[1472] Figure 42-1 shows a curve diagram of animal body weight changes in Example 42;

[1473] Figure 42-2 shows a tumor growth curve in Example 42;

[1474] Figure 42-3 shows a comparison of tumor weights in Example 42;

[1475] Figure 43-1 shows a curve diagram of animal body weight changes in Example 43;

[1476] Figure 43-2 shows a tumor growth curve in Example 43;

[1477] Figure 43-3 shows a comparison of tumor weights in Example 43;

[1478] Figure 44-1 shows the tumor growth curve of the MC38 subcutaneous xenograft tumor model after the start of treatment in Example 44;

[1479] Figure 44-2 shows the curve of animal body weight changes in the MC38 subcutaneous xenograft tumor model after the start of treatment in Example 44;

[1480] Figure 44-3, A shows the binding ratios of different concentrations of CCPD3-Cy5 (0, 100 nM, 200 nM, 500 nM) to monocytes of different species in Example 44, B shows the mean fluorescence intensity of different concentrations of CCPD3-Cy5 (0, 100 nM, 200 nM, 500 nM) binding to monocytes of different species, C shows the binding ratios of different concentrations of CCPD3-Cy5 (0, 100 nM, 200 nM, 500 nM) to lymphocytes of different species, and D shows the mean fluorescence intensity of different concentrations of CCPD3-Cy5 (0, 100 nM, 200 nM, 500 nM) binding to lymphocytes of different species;

[1481] Figure 44-4 shows a graph of mouse body weight changes in the in vivo efficacy test of CCPD3 in the mouse brain glioma GL261-Luc orthotopic tumor model in Example 44;

[1482] Figure 44-5 shows a curve showing the percentage change in mouse body weight in the in vivo efficacy test of CCPD3 in the mouse brain glioma GL261-Luc orthotopic tumor model in Example 44;

[1483] Figures 44-6 to 44-9 show bioluminescent imaging images of each group of mice after tumor inoculation in Example 44, wherein Figure 44-6 is a live imaging image of the dorsal side of a mouse, Figure 44-7 is a live imaging image of the left side of a mouse, Figure 44-8 is a live imaging image of the right side of a mouse, and Figure 44-9 is a live imaging image of the ventral side of a mouse;

[1484] Figure 44-10 shows the BLI value change curves of each group of mice in Example 44, wherein A is the BLI value change curve of the dorsal in vivo imaging of the mouse, B is the BLI value change curve of the left in vivo imaging of the mouse, C is the BLI value change curve of the right in vivo imaging of the mouse, and D is the BLI value change curve of the ventral in vivo imaging of the mouse;

[1485] Figure 44-11 shows the mouse survival curve of the GL261-Luc orthotopic xenograft tumor model in Example 44;

[1486] Figure 44-12 shows the HE staining of brain tissue pathological sections of the GL261-Luc orthotopic xenograft tumor model group in Example 44;

[1487] Figure 44-13 shows the electrophoresis detection diagram of the serum stability test after 100-fold dilution in Example 44; and

[1488] Figure 44-14 shows the electrophoresis detection diagram of the serum stability test in Example 44.

[1489] The corresponding Chinese characters for the English and Chinese characters in the attached drawings are:

[1490] Tumor volume: tumor volume; Days after transplanation: days after inoculation; RTV: relative tumor volume; Tumor weight: tumor weight, left tumor: left tumor, right tumor: right tumor; Days after incubation: days after incubation; control: control; Mean Value: mean value; concentration: concentration; Body weight: body weight; lymphocytes: lymphocytes; monocytes: monocytes; negative control: negative control; radiance: radiation rate; color scale: color scale; Percent survival: survival rate; Days after tumor incubation: days after tumor incubation; Total flux: total flux.

[1491] The "CD40" portion in the accompanying drawings is an abbreviation of the "CD40 aptamer" described in the Examples and has the same meaning as "Apt CD40" in Table 5. Similar examples also include MUC1, CD16a, CTLA-4, PD-L1, C12, TTA1, AS1411, A15, PSMA, FAP, CD16a, Act-12c, PD1, Her2, Her3, VEGF, N48, CD3-4, PD-1, BCMA, CD38, FGF2, HBsAg, CPG, and CD-19. "Bio" is equivalent to "biotin," and "survivin" is equivalent to "survivin iRNA." DETAILED DESCRIPTION

[1492] It should be noted that, in the absence of conflict, the embodiments and features of the embodiments in this application can be combined with each other. The present invention will be described in detail below with reference to the accompanying drawings and in combination with the embodiments.

[1493] Explanation of terms:

[1494] Oligonucleotide refers to an oligonucleotide molecule including small interfering nucleic acid (siRNA), antisense nucleic acid (ASO), microRNA (miRNA) and nucleic acid aptamer (Aptamer). Oligonucleotide drugs are composed of nucleotides and are a completely new drug category that is completely different from small molecule drugs and antibody drugs. Compared with traditional chemical drug molecules, oligonucleotide drugs have the advantages of strong target specificity, high efficiency, long-lasting drug effect, simple drug design, and rich candidate targets. The main oligonucleotide drugs are siRNA drugs and antisense nucleic acid drugs, which mainly act on cytoplasmic mRNA, recognize and inhibit target mRNA through base complementarity, realize the regulation of protein expression, and achieve the purpose of treating diseases. The nucleic acid or small nucleic acid of this application refers to small nucleic acids.

[1495] Antisense oligonucleotides (ASOs): ASOs, or antisense oligonucleotides, are typically short (16-53 nucleotides), synthetic oligonucleotides designed to block the function of RNA (including mRNA or miRNA). These nucleotides are typically highly complementary to small RNAs and may contain chemically modified nucleotides or have specific sequences added to their ends to increase their binding affinity and resist intracellular nucleic acid degradation.

[1496] When targeting mRNA, ASOs are typically designed to form complementary pairs with specific regions of the target mRNA to prevent reading by the translation machinery, cause mRNA degradation, or modify mRNA splicing.

[1497] When targeting miRNA, ASOs (also called anti-miRNA molecules based on their function) are typically designed to form a complementary pair with a specific miRNA, preventing the miRNA from binding to its target mRNA, thereby inhibiting the function of the miRNA (miRNA is a class of short non-coding RNAs that can form a complementary pair with the 3' untranslated region of the target mRNA, thereby affecting the stability and translation of the mRNA and further regulating protein expression). ASOs that act as anti-miRNA molecules in this application include, but are not limited to, A-miR21, A-miR-10a, A-miR-30c, AmiR1306, and the like.

[1498] MicroRNA (miRNA): A short, non-coding RNA approximately 22 nucleotides in length. Its mechanism of action is to form complementary pairs with the 3' untranslated region (3'UTR) of target mRNAs, thereby regulating the stability or translation of target mRNAs, thereby affecting protein expression. MiRNAs have been shown to play a key role in many biological processes, including development, differentiation, proliferation, and apoptosis.

[1499] MicroRNAs exist in various forms, the most primitive of which is pri-miRNA. Pri-miRNA undergoes a single process to become pre-miRNA, or a microRNA precursor. Pre-miRNA is then cleaved by the Dicer enzyme into mature miRNA. In actual research, pre-miRNAs are the earliest and most widely used, with many commercial microRNA libraries being in pre-miRNA form. Recent studies have also revealed that the arms of microRNAs play a crucial role in the formation of mature miRNAs, leading to an increasing use of the natural pri-miRNA form.

[1500] In addition, as part of a therapeutic strategy, in order to increase the level of specific miRNAs (such as miR-34a or miR-122) in the body, existing studies have proposed the concept of miRNA supplements. Such supplements are usually miRNA analogs or mimics, which can be in RNA form or DNA form. When in DNA form, as long as they can be transcribed into RNA with the same sequence, they can perform the same function as normal miRNAs in cells.

[1501] Using DNA sequences as miRNA supplements has several advantages. First, DNA is more stable and resistant to degrading enzymes in the body. Second, DNA can be read by the cell's transcription machinery and transcribed into the corresponding RNA, thereby increasing miRNA levels within the cell. Finally, DNA synthesis is relatively easy and inexpensive, making it easier to design and manufacture, especially for large-scale production and application.

[1502] Taking miR-34a as an example, miR-34a has been shown to play an important anti-tumor role in many types of cancer. Therefore, increasing miR-34a levels in the body may be an effective cancer treatment strategy. By providing miR-34a supplements in the form of DNA sequences (i.e., miRNA mimics), miR-34a levels in the body can be increased, thereby inhibiting the growth and survival of cancer cells.

[1503] Therefore, in the application, the meaning of miRNA is broad, including various forms, such as the above-mentioned pri-miRNA, pre-miRNA, mature miRNA and miRNA analogs (DNA form, which can form oligonucleotides with the same sequence and the same function as mature miRNA through transcription). In this application, miRNA analogs include but are not limited to one or more of miR-34, miR-542, miR-126 and miR-122.

[1504] Chemical modifications at specific positions in oligonucleotide drugs can improve the stability of these small nucleic acid molecules and avoid stimulating immune system responses. The chemical modifications involved in oligonucleotide drugs in this application include but are not limited to the following aspects:

[1505] 1) Backbone modification: Sulfosuccinate (PS) bond modification is achieved by replacing a non-bridging oxygen in the phosphodiester with a sulfur atom. The PS linkage makes the modified oligonucleotide resistant to nucleases. Compared with unmodified oligonucleotides, these oligonucleotides are more easily bound to plasma proteins, thereby extending their half-life.

[1506] 2) Ribose modification: Ribose modification refers to the replacement of the 2'-OH group of the ribose sugar on a nucleotide with 2'-F, 2'-OMe, or 2'-O-MOE. This modification can affect the affinity of small nucleic acids for target RNA, their stability to ribozymes, and their properties after binding to RNA. Currently, the most commonly used modification is 2'-O-methoxyethyl (2'-O-MOE).

[1507] 3) Base modification: Modification of bases can enhance the interaction between oligonucleotide drugs and mRNA bases. Currently, the only widely used base modification is the C5 methyl substitution (5-methylcytosine) on the pyrimidine ring.

[1508] Although there are a variety of carriers in the prior art that improve drug delivery efficiency, including nucleic acid carriers, it is still difficult to solve the problem of limited clinical application of drugs. In order to solve the above problems, the present invention provides a nucleic acid vector, which comprises a sequence a, a sequence b and a sequence c, and the nucleic acid vector is selected from any one of the following DNA vectors, RNA vectors, or DNA-RNA hybrid vectors; wherein the sequence a, the sequence b and the sequence c self-assemble to form the nucleic acid vector, the sequence a, the sequence b and the sequence c comprise a vector backbone sequence, and the vector backbone sequence comprises the following core sequences: a1 sequence, b1 sequence and c1 sequence, or any variant sequence of at least one of the a1 sequence, b1 sequence and c1 sequence, the variant sequence comprising an insertion, deletion or substitution of at least one base; wherein, in the DNA vector, the a1 sequence is SEQ ID NO: 1, the b1 sequence is SEQ ID NO: 2, and the c1 sequence is SEQ ID NO: 3; in the RNA vector, the a1 sequence is SEQ ID NO: 4, the b1 sequence is SEQ ID NO: 5, and the c1 sequence is SEQ ID NO: 6; the DNA-RNA hybrid vector is a vector self-assembled by a combination of the sequences of the DNA vector and the sequences of the RNA vector.

[1509] SEQ ID NO: 1: ACGAGCGTTCCG;

[1510] SEQ ID NO: 2: CGGTTCGCCG;

[1511] SEQ ID NO:3: CGGCCATAGCCGT;

[1512] SEQ ID NO: 4: ACGAGCGUUCCG;

[1513] SEQ ID NO: 5: CGGUUCGCCG;

[1514] SEQ ID NO:6: CGGCCAUAGCCGU.

[1515] The nucleic acid vector in the above-mentioned preferred embodiment is formed by the sequence self-assembly comprising the above-mentioned core sequence, forms a three-dimensional nanostructure by self-assembly, can effectively reduce or prevent the degradation of nuclease, improves the stability of the vector. The nucleic acid nanoparticles formed by the self-assembly of three single-stranded core sequences listed in the application are used as the delivery vector of oligonucleotide drugs, compared to LNP and PNP in the prior art, because the vector itself and the medicine delivered are nucleotide sequences, in physicochemical properties, the compatibility with oligonucleotide drugs is stronger, it is convenient to mount different types of small nucleic acid molecules according to the difference of the vector sequence structure or its length, and utilize the combined advantage of base complementary pairing, not only improve delivery efficiency, but also make delivery system more stable. Moreover, the nucleic acid vector with the above-mentioned core sequence itself has certain immunostimulation, and when used as the delivery vector of nucleic acid drugs, not only plays a carrier effect, but also can promote the effect of nucleic acid drugs drug effect to a certain extent. In addition, nucleic acid vector is also simpler and more efficient in preparation technology.

[1516] In the above-mentioned nucleic acid vector, according to the length of the oligonucleotide drug molecule sequence to be delivered subsequently, the length of the three sequences can also be appropriately extended to further improve the stability after the oligonucleotide drug is mounted. In a preferred embodiment of the present application, the above-mentioned carrier backbone sequence also includes a first extension segment and an optional second extension segment, and the first extension segment and the second extension segment are located at the 5' end and / or 3' end of any sequence in the a1 sequence, the b1 sequence and the c1 sequence. Preferably, the length of the first extension segment and the second extension segment are each independently 1 to 14nt as needed, preferably 1-10nt, more preferably 2-7nt, and further preferably 3-7nt. Specifically, it can be 1nt, 2nt, 3nt, 4nt, 5nt, 6nt, 7nt, 8nt, 9nt, 10nt, 11nt, 12nt, 13nt or 14nt.

[1517] In some preferred embodiments, the first extension segment is selected from any one or more of the following DNA extension segments or RNA extension segments corresponding to the DNA extension segment:

[1518] 1) 5' end of the a1 sequence: GACGCCC, 3' end of the c1 sequence: GGGCGTC; or the RNA extension corresponding to the DNA extension in 1);

[1519] 2) 3' end of the a1 sequence: GGAGAGG, 5' end of the b1 sequence: CCTCTCC; or the RNA extension corresponding to the DNA extension in 2);

[1520] 3) 3' end of the b1 sequence: CGAGCC, 5' end of the c1 sequence: GGCTCG or GGCACG; or the RNA extension corresponding to the DNA extension in 3);

[1521] 4) 5' end of the a1 sequence: GGCGCCC or GACGCCC, 3' end of the c1 sequence: GGGCGCC; or the RNA extension corresponding to the DNA extension in 4);

[1522] 5) 3' end of the a1 sequence: GGAG, 5' end of the b1 sequence: CTCC; or the RNA extension corresponding to the DNA extension in 5);

[1523] 6) The 3' end of the b1 sequence is CCAGCC, and the 5' end of the c1 sequence is GGCACG or GGCTCG; or the RNA extension corresponding to the DNA extension in 6).

[1524] Preferably, the second extension segment is selected from any one or more of the following DNA extension segments or RNA extension segments corresponding to the DNA extension segment:

[1525] 1) The 5' end of the a1 sequence: C or GC, the 3' end of the c1 sequence: GC or GCT; or the RNA extension corresponding to the DNA extension in 1);

[1526] 2) 3' end of the a1 sequence: AG, AGC, or AGCT, 5' end of the b1 sequence: GCT or CT; or the RNA extension corresponding to the DNA extension in 2);

[1527] 3) 3' end of the b1 sequence: GC, GCG, or GCGT, 5' end of the c1 sequence: GC or CGC; or the RNA extension corresponding to the DNA extension in 3);

[1528] 4) 3' end of the a1 sequence: C, AGGCC, AGGCCT, or AGGAG, 5' end of the b1 sequence: G, GGCCT, or CTCCT; or the RNA extension corresponding to the DNA extension in 4);

[1529] 5) The 3' end of the b1 sequence is GCC or GCCT, and the 5' end of the c1 sequence is GGC; or it is the RNA extension corresponding to the DNA extension in 5).

[1530] Adding the above-mentioned extension segments of different lengths helps to further improve the stability of different nucleic acid vectors carrying effector molecules of different molecular weights, and also facilitates the selection of appropriate nucleic acid vectors according to the different nucleic acid effector molecules mounted.

[1531] It should be noted that the vector backbone sequence in the present application includes the aforementioned a1 sequence, b1 sequence and c1 sequence (or variant sequences of the three) and the aforementioned optional first extension segment and second extension segment. On the basis of such a vector backbone sequence, in certain embodiments, in order to further improve the stability of the small nucleic acid effector molecules of different sequence lengths, the above-mentioned nucleic acid vector may further include a single-stranded bonding bridge sequence and / or a transition sequence, wherein the single-stranded bonding bridge sequence is selected from any one or more of the following: located at the core sequence of sequence a: 3' end: SEQ ID NO: 7: TGTAGCACGGTGGC or its complementary sequence SEQ ID NO: 8: GCCACCGTGCTACA; located at the core sequence of sequence b: 3' end: SEQ ID NO: 9: TCGGCGCGGCCGTG or its complementary sequence SEQ ID NO: 10: CACGGCCGCGCCGA; located at the core sequence of sequence c: 3' end: SEQ ID NO: 11: TGCTGCTGCTGCTG or its complementary sequence SEQ ID NO: 12: CAGCAGCAGCAGCA; the transition sequence is a sequence formed by n consecutive U, T or A, n is a natural number of 2 to 8, preferably 3-6, or a sequence of a random combination of A, U, T, C and / or G, and the transition sequence is located at the 5' end or 3' end of the core sequence.

[1532] The above-mentioned single-stranded connecting bridge sequence and its complementary sequence are designed to connect the oligonucleotide effector molecule to the nucleic acid vector sequence by complementary pairing. Therefore, according to the specific vector core sequence and the specific sequence of the oligonucleotide effector molecule, a single-stranded connecting bridge sequence composed of an appropriate number and appropriate sequence is selected.

[1533] In certain embodiments, to facilitate the synthesis of nucleic acid vectors and / or oligonucleotide drugs and reduce the cost of nucleic acid synthesis, the sequence of the nucleic acid vector is configured as a vector backbone sequence + a single-stranded bridge sequence. This facilitates the simultaneous formation of the vector and the attachment of the oligonucleotide drug by synthesizing a sequence complementary to the single-stranded bridge sequence at the end of the vector during synthesis. This also avoids the problems of long fragments, high synthesis difficulty, and high cost associated with directly synthesizing the nucleic acid sequence of the vector and the nucleic acid sequence of the oligonucleotide drug.

[1534] In certain preferred embodiments, the a sequence, b sequence, and c sequence in the nucleic acid vector are as follows:

[1535] a sequence is: SEQ ID NO: 15:

[1536] GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC, where the underlined portion is the single-stranded connecting bridge sequence A;

[1537] The b sequence is: SEQ ID NO: 16: CCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, wherein the underlined portion is the single-stranded connecting bridge sequence B;

[1538] The c sequence is: SEQ ID NO: 17:

[1539] GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG, wherein the underlined portion is the single-stranded connecting bridge sequence C.

[1540] It should be noted that the above-mentioned single-stranded connecting bridge sequence is not always present on sequence a, sequence b, and sequence c of the nucleic acid vector at the same time, and can be selected according to actual needs. For example, it can be present only on sequence a, only on sequence b, only on sequence c, or only on sequence a and sequence b, only on sequence a and sequence c, or only on sequence c and sequence b.

[1541] In other embodiments, the sequence a, sequence b, and sequence c in the nucleic acid vector are as follows:

[1542] a sequence is: SEQ ID NO: 18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC;

[1543] b sequence is: SEQ ID NO: 19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG;

[1544] The c sequence is: SEQ ID NO: 20:

[1545] CAGCAGCAGCAGCACGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the underlined part is the single-stranded connecting bridge sequence.

[1546] It should be noted that, depending on whether the small nucleic acid drug to be mounted on the nucleic acid carrier is siRNA, miRNA or nucleic acid aptamer, the specific way of mounting it on the nucleic acid carrier is also different. For example, when a nucleic acid aptamer is mounted, it can be connected to any end of any one or more sequences in the a, b or c sequence through a transition sequence or a single-stranded bridge sequence, or the miRNA can be used as a transition sequence to connect the nucleic acid aptamer sequence to any end of any sequence in the a, b or c sequence (for example, when the miRNA sequence is set at the 5' end of the a sequence, the nucleic acid aptamer sequence can be set at the 5' end of the miRNA sequence; similarly, when the miRNA sequence is set at the 3' end of the b sequence, the nucleic acid aptamer sequence is set at the 3' end of the miRNA sequence;). It should be noted here that when the nucleic acid aptamer sequence is connected through a transition sequence or a miRNA sequence, it is a covalent connection. When connected through a single-stranded bridge sequence, the connection is achieved by complementary pairing with the complementary sequence of the single-stranded bridge provided (i.e., covalently linked) on the a, b, or c sequence. This is a connection method based on intermolecular forces, rather than a chemical covalent connection method. Similarly, when siRNA is mounted, the antisense strand of the siRNA is connected by complementarity with the sense strand provided (i.e., covalently linked) on the a, b, or c sequence. The connection of the sense strand is usually also connected through a transition sequence. In some cases, when the nucleic acid aptamer is in the form of RNA, similar to miRNA, it can also be covalently linked directly to the a, b, or c sequence without a transition sequence. Or it can be covalently linked to the a, b, or c sequence only through individual TT, AA, or UU or a single U or A.

[1547] In some preferred embodiments, the core sequences for self-assembly to form nucleic acid vectors are selected from any of the following groups:

[1548] 1) a sequence: SEQ ID NO: 21: GCGACGCCCACGAGCGTTCCGGGAGAGGAG,

[1549] b Sequence: SEQ ID NO:22: CTCCTTCCCGGTTCGCCGCGAGCCGCG,

[1550] c sequence: SEQ ID NO: 23: CGCGGCACGCGGCCATAGCCGTGGGCGTCGC;

[1551] 2) a sequence: SEQ ID NO: 24: GCGACGCCCACGAGCGTTCCGGGAGAGGAGCT,

[1552] b sequence: SEQ ID NO:19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG,

[1553] c sequence: SEQ ID NO:23: CGCGGCACGCGGCCATAGCCGTGGGCGTCGC;

[1554] 3) a sequence: SEQ ID NO:24: GCGACGCCCACGAGCGTTCCGGGAGAGGAGCT,

[1555] b sequence: SEQ ID NO:25: GCTCCTCTCCCGGTTCGCCGCGAGCCGCGT,

[1556] c sequence: SEQ ID NO:26: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGCT;

[1557] 4) a sequence: SEQ ID NO:24: GCGACGCCCACGAGCGTTCCGGGAGAGGAGCT,

[1558] b sequence: SEQ ID NO:25: GCTCCTCTCCCGGTTCGCCGCGAGCCGCGT,

[1559] c sequence: SEQ ID NO:27: CGCGGCACGCGGCCATAGCCGTGGGCGTCGCT;

[1560] 5) a sequence: SEQ ID NO:28: GACGCCCACGAGCGTTCCGGGAGAGG,

[1561] b sequence: SEQ ID NO:29: CCTCTCCCGGTTCGCCGCGAGCC,

[1562] c sequence: SEQ ID NO:30: GGCTCGCGGCCATAGCCGTGGGCGTC;

[1563] 6) a sequence: SEQ ID NO:18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC,

[1564] b sequence: SEQ ID NO:19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG, <00c sequence: SEQ ID NO:31: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGC;

[1566] 7) a sequence: SEQ ID NO:24: GCGACGCCCACGAGCGTTCCGGGAGAGGAGCT,

[1567] b sequence: SEQ ID NO:19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG,

[1568] c sequence: SEQ ID NO:26: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGCT;

[1569] 8) a sequence: SEQ ID NO:24: GCGACGCCCACGAGCGTTCCGGGAGAGGAGCT,

[1570] b sequence: SEQ ID NO:19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG,

[1571] c sequence: SEQ ID NO:31: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGC;

[1572] 9) a sequence: SEQ ID NO:24: GCGACGCCCACGAGCGTTCCGGGAGAGGAGCT,

[1573] b sequence: SEQ ID NO:25: GCTCCTCTCCCGGTTCGCCGCGAGCCGCGT,

[1574] c sequence: SEQ ID NO:26: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGCT;

[1575] 10) a sequence: SEQ ID NO:24: GCGACGCCCACGAGCGTTCCGGGAGAGGAGCT,

[1576] b sequence: SEQ ID NO:25: GCTCCTCTCCCGGTTCGCCGCGAGCCGCGT,

[1577] c sequence: SEQ ID NO:31: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGC;

[1578] 11) Sequence a: SEQ ID NO:18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC,

[1579] Sequence b: SEQ ID NO:25: GCTCCTCTCCCGGTTCGCCGCGAGCCGCGT,

[1580] Sequence c: SEQ ID NO:26: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGCT;

[1581] 12) Sequence a: SEQ ID NO:32: CGACGCCCACGAGCGTTCCGGGAGAGGAGC;

[1582] Sequence b: SEQ ID NO:19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG;

[1583] Sequence c: SEQ ID NO:31: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGC;

[1584] 13) Sequence a: SEQ ID NO:33: GCGGCGCCCACGAGCGTTCCGGGAGC; <00!

[1585] Sequence b: SEQ ID NO:34: GCTCCCGGTTCGCCGCCAGCCGCC;

[1586] Sequence c: SEQ ID NO:35: GGCGGCAGGCGGCCATAGCCGTGGGCGCCGC;

[1587] 14) Sequence a: SEQ ID NO:36: GCGGCGCCCACGAGCGTTCCGGGAGAGGCC;

[1588] Sequence b: SEQ ID NO:37: GGCCTCTCCCGGTTCGCCGCCAGCCGCC;

[1589] Sequence c: SEQ ID NO:38: GGCGGCTGGCGGCCATAGCCGTGGGCGCCGC;

[1590] 15) Sequence a: SEQ ID NO:39: GCGGCGCCCACGAGCGTTCCGGGAGAGGCCT;

[1591] b sequence: SEQ ID NO:40: GGCCTCTCCCGGTTCGCCGCCAGCCGCCT;

[1592] c sequence: SEQ ID NO:41: GGCGGCTGGCGGCCATAGCCGTGGGCGCCGCT;

[1593] 16) a sequence: SEQ ID NO:42: GCGGCGCCCACGAGCGUUCCGGGAGAGGCC;

[1594] b sequence: SEQ ID NO:43: GGCCUCUCCCGGUUCGCCGCCAGCCGCC;

[1595] c sequence: SEQ ID NO:44: GGCGGCUGGCGGCCAUAGCCGUGGGCGCCGC;

[1596] 17) a sequence: SEQ ID NO:45: CGACGCCCACGAGCGTTCCGGGAGAGGAG;

[1597] b sequence: SEQ ID NO:46: CTCCTCTCCCGGTTCGCCGCCAGCCGCC;

[1598] c sequence: SEQ ID NO:35: GGCGGCAGGCGGCCATAGCCGTGGGCGCCGC;

[1599] 18) a sequence: SEQ ID NO:36: GCGGCGCCCACGAGCGTTCCGGGAGAGGCC;

[1600] b sequence: SEQ ID NO:43: GGCCUCUCCCGGUUCGCCGCCAGCCGCC;

[1601] c sequence: SEQ ID NO:44: GGCGGCUGGCGGCCAUAGCCGUGGGCGCCGC;

[1602] 19) a sequence: SEQ ID NO:36: GCGGCGCCCACGAGCGTTCCGGGAGAGGCC;

[1603] b sequence: SEQ ID NO:40: GGCCTCTCCCGGTTCGCCGCCAGCCGCCT;

[1604] c sequence: SEQ ID NO:38: GGCGGCTGGCGGCCATAGCCGTGGGCGCCGC;

[1605] 20) a sequence: SEQ ID NO:36: GCGGCGCCCACGAGCGTTCCGGGAGAGGCC;

[1606] b sequence: SEQ ID NO:40: GGCCTCTCCCGGTTCGCCGCCAGCCGCCT;

[1607] c sequence: SEQ ID NO:41: GGCGGCTGGCGGCCATAGCCGTGGGCGCCGCT;

[1608] 21) a sequence: SEQ ID NO:36: GCGGCGCCCACGAGCGTTCCGGGAGAGGCC;

[1609] b sequence: SEQ ID NO:37: GGCCTCTCCCGGTTCGCCGCCAGCCGCC;

[1610] c sequence: SEQ ID NO:44: GGCGGCUGGCGGCCAUAGCCGUGGGCGCCGC;

[1611] 22) a sequence: SEQ ID NO:33: GCGGCGCCCACGAGCGTTCCGGGAGC;

[1612] b sequence: SEQ ID NO:46: CTCCTCTCCCGGTTCGCCGCCAGCCGCC;

[1613] c sequence: SEQ ID NO:35: GGCGGCAGGCGGCCATAGCCGTGGGCGCCGC;

[1614] 23) a sequence: SEQ ID NO:47: GCGGCGCCCACGAGCGTTCCGGGAGAGGAG; <​​​​​​24) a sequence: SEQ ID NO: 48: CGCCCACGAGCGTTCCGGGAGA;

[1618] b sequence: SEQ ID NO: 49: TCTCCCGGTTCGCCGCGAG;

[1619] c sequence: SEQ ID NO: 50: CTCGCGGCCATAGCCGTGGGCG;

[1620] 25) a sequence: SEQ ID NO: 51: UCGCCCACGAGCGUUCCGGGAGA;

[1621] b sequence: SEQ ID NO: 52: UCUCCCGGUUCGCCGCGAG;

[1622] c sequence: SEQ ID NO: 53: UCUCGCGGCCAUAGCCGUGGGCG;

[1623] 26) a sequence: SEQ ID NO: 54: GCGCCCACGAGCGTTCCGGGAGAGC;

[1624] b Sequence: SEQ ID NO: 55: CCCUGCTCTCCCGGTTCGCCGCCAGCCGCC;

[1625] c sequence: SEQ ID NO: 56: GGCGGCAGGCGGCCATAGCCGTGGGCGC.

[1626] The nucleic acid vectors self-assembled according to the core sequences of different compositions can adapt to the mounting of different types of oligonucleotide drugs, and different types of oligonucleotide drugs can also be mounted on the same nucleic acid vector, thereby improving the mounting type and efficiency of oligonucleotide drugs.

[1627] It should be noted that, in order to further reduce the susceptibility of the aforementioned nucleic acid nanoparticles to RNase degradation and improve stability during delivery, certain sites on the nucleic acid vector can be modified in certain cases. In some preferred embodiments, at least one of the bases, ribose, and phosphate groups in sequences a, b, and c has at least one modifiable site, and any modifiable site has at least one of the following modifications: -F, methyl, amino, disulfide, carbonyl, carboxyl, sulfhydryl, aldehyde, and thio. Preferably, some bases in sequences a, b, and c have thio modifications. When the modification site is a thiol, it is considered a thio modification, which has a weaker modification strength and is low-cost, and can improve the stability of the RNA sequence and the RNA vector or DNA-RNA hybrid vector assembled therefrom. To further improve stability, in the RNA-containing nucleic acid vector, the RNA contains both 2'-F and 2'-OMe modifications, more preferably 2'-F modifications on U and C, and 2'-OMe modifications on A and G.

[1628] In a second typical embodiment of the present application, a nucleic acid drug is provided, which includes the above-mentioned nucleic acid vector and a bioactive substance mounted on the nucleic acid vector, the bioactive substance including an oligonucleotide effector molecule and a targeting molecule for targeted delivery of the oligonucleotide molecule, wherein the oligonucleotide effector molecule is selected from at least one of the following: a nucleic acid immunostimulant, a nucleic acid aptamer, siRNA, miRNA and ASO; and when the oligonucleotide effector molecule includes a nucleic acid aptamer, the targeting molecule at least includes a nucleic acid aptamer; when the oligonucleotide effector molecule does not include a nucleic acid aptamer, the targeting molecule at least includes a small molecule compound with a targeting effect.

[1629] The above-mentioned nucleic acid drug of the present application addresses 1) the problem of compounding multiple oligonucleotide drugs into drugs; and 2) the problem of systematic preparation of nano-nucleic acid drugs with relatively complex structures. Based on the aforementioned improved nano-nucleic acid carrier structure, by adopting different mounting strategies to mount one or more oligonucleotide effector molecules, it not only provides an integrated drug of multiple oligonucleotide drugs, but also provides a new idea and implementation path for the drug construction of such oligonucleotide drugs.

[1630] The nucleic acid immunostimulatory agent in this application is an immunostimulatory factor: tumor cells low expression of major histocompatibility complex (MHC) molecules, lack of co-stimulatory molecules, antigen processing defects and changes in the expression of T cell signaling molecules, etc., which cause the body's anti-tumor immunity to be low and are the main cause of tumor occurrence and development.

[1631] CPG ODN (CpG oligonucleotide, CpG oligodeoxynucleotide) is a synthetic oligodeoxynucleotide (ODN) containing unmethylated cytosine guanine dinucleotide (CpG), which can simulate bacterial DNA to stimulate immune cells of various mammals, including humans.

[1632] Different types of CpG ODN have different structural characteristics and immune effects, and are generally divided into three categories: A, B, and C.

[1633] Class A CpG ODN has a palindromic sequence containing CpG dinucleotides as its core, with poly G tails at both ends and a partially thiolated phosphodiester bond backbone. It forms a higher-order structure through the palindromic sequence and poly G, which can activate plasmacytoid dendritic cells to induce large amounts of type I interferon, but has weak activity against B cells.

[1634] Class B CpG ODN is a fully thiolated linear CpG ODN that has strong immunostimulatory activity on B cells but cannot activate plasmacytoid dendritic cells.

[1635] Class C CpG-ODN is a type of fully thiolated CpG ODN that can form dimers through palindromic sequences. It has the activity of both type A and type B CpG-ODN and can activate both plasmacytoid dendritic cells and B cells.

[1636] The aforementioned nucleic acid immunostimulants refer to DNA or synthetic oligonucleotides containing CpG motifs. They can activate various immune cells, such as dendritic cells, natural killer cells, B cells, and T cells, induce the secretion of Th1 cytokines, primarily interleukin-12, upregulate the expression of co-stimulatory molecules, and induce Th1 immune responses. Therefore, they have important application value in anti-tumor applications. Therefore, all existing CpG immunostimulants are suitable for this application. In a preferred embodiment of the present application, the nucleic acid immunostimulator includes one or more of CpG2006, a variant of CpG2006, CpG1826, CpG2216, CpG2395 and CpG-ODNT7; more preferably, the sequence of CpG2006 is: SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT or SEQ ID NO: 58: UCGUCGUUUUGUCGUUUUGUCGUU; preferably, the sequence of the variant of CpG2006 is: GTCGTT; preferably, the sequence of CpG1826 is: SEQ ID NO: 59: TCCATGACGTTCCTGACG; preferably, the sequence of CpG2216 is: SEQ ID NO: 60: GGGGGACGATCGTCGGGGG; preferably, the sequence of CpG2395 is: SEQ ID NO:61: TCGTCGTTTTCGGCGCGCGCCG; preferably, the sequence of CpG-ODNT7 is: SEQ ID NO:62: TCGTCGTCGTCGTCGTCGTCG or SEQ ID NO:63: TCGTCGTCGTCGTCGTCGTCGTCG; preferably, the nucleic acid immunostimulator further comprises CpG-BYZD: AGCGAA.

[1637] The aforementioned siRNA can be any currently known siRNA drug. In a preferred embodiment of the present application, it includes but is not limited to siRNA of any one or more of the following molecules: ASAP1, ATAD2, CD24, CD47, EGFR, HBV, HSP, HS70, PD-L1, PAPP-1, Survivin, TAP, TIM-3, TGF-β1, and VEGF-C. All existing siRNAs of the aforementioned molecules are suitable for use in the present application.

[1638] More preferably, the siRNA of ASAP1 is selected from any one of the following: i) sense strand: SEQ ID NO: 64: AUUUGCUUCCAUAAUAUCAUU, antisense strand: SEQ ID NO: 65: UGAUAUUAUGGAAGCAAAUUU. ii) sense strand: SEQ ID NO: 66: UUAGGUUUGGGGUUGGAUCUU, antisense strand: SEQ ID NO: 67: GAUCCAACCCCAAACCUAAUU.

[1639] More preferably, the antisense strand of the siRNA of ATAD2 is SEQ ID NO: 68: GCGUCGAAGUUGUAGGAUUUU, and the sense strand is SEQ ID NO: 69: AAUCCUACAACUUCGACGCUU.

[1640] More preferably, the sense strand of the CD24 siRNA is SEQ ID NO: 70: UGUUUACAUUGUUGAGGUAUU, and the antisense strand is SEQ ID NO: 71: UACCUCAACAAUGUAAACUUU.

[1641] More preferably, the siRNA for CD47 is selected from any one of the following: i) sense chain: SEQ ID NO: 72: GGUGAUUACCCAGAGAUAUTT, antisense chain: SEQ ID NO: 73: AUAUCUCUGGGUAAUCACCTT; ii) sense chain: SEQ ID NO: 74: UGGUGAAAGAGGUCAUUCCUU, antisense chain: SEQ ID NO: 75: GGAAUGACCUCUUUCACCAUU; iii) sense chain: SEQ ID NO: 76: GGAAUGACCUCUUUCACCATT, antisense chain: SEQ ID NO: 77: UGGUGAAAGAGGUCAUUCCTT; iv) sense chain: SEQ ID NO: 78: GGUGAUUACCCAGAGAUAUUU, antisense chain: SEQ ID NO: 79: AUAUCUCUGGGUAAUCACCUU;

[1642] Preferably, the siRNA for EGFR is selected from any one of the following: i) sense chain: SEQ ID NO: 80: GGCUGGUUAUGUCCUCAUUUU, antisense chain: SEQ ID NO: 81: AAUGAGGACAUAACCAGCCUU; ii) sense chain: SEQ ID NO: 82: CCUUAGCAGUCUUAUCUAAUU, antisense chain: SEQ ID NO: 83: UUAGAUAAGACUGCUAAGGUU; iii) sense chain: SEQ ID NO: 84: UGCCUUAGCAGUCUUAUCUAAUU, antisense chain: SEQ ID NO: 85: UUAGAUAAGACUGCUAAGGCAUU; iv) sense chain: SEQ ID NO: 86: UGCCUUAGCAGUCUUAUCUAAUUU, antisense chain: SEQ ID NO: 87: AAUUAGAUAAGACUGCUAAGGCAUU;

[1643] Preferably, the sense strand of the HBV siRNA is: SEQ ID NO: 88: GGACUUCUCUCAAUUUUCUUU, and the antisense strand is: SEQ ID NO: 89: AGAAAAUUGAGAGAAGUCCUU;

[1644] Preferably, the sense strand of the siRNA of HSP is: SEQ ID NO: 90: CGCAGAACCGUGUUCGAUU, and the antisense strand is: SEQ ID NO: 91: UCGAACACGGUGUUCUGCGUU;

[1645] Preferably, the sense strand of the siRNA of HS70 is: SEQ ID NO: 92: GGCCAACAAGAUCACCAUCUU, and the antisense strand is: SEQ ID NO: 93: GAUGGUGAUCUUGUUGGCCUU;

[1646] Preferably, the siRNA for PD-L1 is selected from any one of the following: i) sense chain: SEQ ID NO: 94: CCAGCACACUGAGAAUCAAUU, antisense chain: SEQ ID NO: 95: UUGAUUCUCAGUGUGCUGGUU; ii) sense chain: SEQ ID NO: 96: AGACGUAAGCAGUGUUGAATT, antisense chain: SEQ ID NO: 97: UUCAACACUGCUUACGUCUTT;

[1647] Preferably, the siRNA for PARP-1 is: sense strand: SEQ ID NO: 98: GAGGAAGGUAUCAACAAAUTT, antisense strand: SEQ ID NO: 99: AUUUGUUGAUACCUUCCUCTT;

[1648] Preferably, the siRNA of Survivin is selected from any one of the following: i) sense chain: SEQ ID NO: 100: GCAGGUUCCUUAUCUGUCACAUU, antisense chain: SEQ ID NO: 101: UGUGACAGAUAAGGAACCUGCUU; ii) sense chain: SEQ ID NO: 102: GGAAUUGGAAGGCUGGGAACCUU, antisense chain: SEQ ID NO: 103: GGUUCCCAGCCUUCCAAUUCCUU; iii) sense chain: SEQ ID NO: 104: UGCAGGUUCCUUAUCUGUCATT, antisense chain: SEQ ID NO: 105: UGACAGAUAAGGAACCUGCTT; iv) sense chain: SEQ ID NO: 106: CUGCAGGUUCCUUAUCUGUCACAUU, antisense chain: SEQ ID NO: 107: UGUGACAGAUAAGGAACCUGCAGUU;

[1649] Preferably, the siRNA of TAP is selected from any one of the following: i) sense chain: SEQ ID NO: 108: GCUGCACACGGUUCAGAAUUU, antisense chain: SEQ ID NO: 109: AUUCUGAACCGUGUGCAGCUU; ii) sense chain: SEQ ID NO: 110: CAGGAUGAGUUACUUGAAAUU, antisense chain: SEQ ID NO: 111: UUUCAAGUAACUCAUCCUGUU

[1650] Preferably, the sense strand of the TIM-3 siRNA is: SEQ ID NO: 112: GUGCUCAGGACUGAUGAAATT, and the antisense strand is: SEQ ID NO: 113: UUUCAUCAGUCCUGAGCACTT;

[1651] Preferably, the siRNA of TGF-β1 is selected from any one of the following: i) sense chain: SEQ ID NO: 114: GUCAACUGUGGAGCAACACUU, antisense chain: SEQ ID NO: 115: GUGUUGCUCCACAGUUGACUU; ii) sense chain: SEQ ID NO: 116: GCAACAACGCCAUCUAUGATT, antisense chain: SEQ ID NO: 117: UCAUAGAUGGCGUUGUUGCTT;

[1652] Preferably, the siRNA of VEGF-C is selected from any one of the following: i) sense chain: SEQ ID NO: 118: GCAAGACGUUGUUUGAAAUUAUU, antisense chain: SEQ ID NO: 119: UAAUUUCAAACAACGUCUUGCUU; ii) sense chain: SEQ ID NO: 120: CAGCAAGACGUUGUUUGAAAUUAUU, antisense chain: SEQ ID NO: 121: UAAUUUCAAACAACGUCUUGCUGUU; iii) sense chain: SEQ ID NO: 122: CAGGAUGGUAAAGACUACAUU, antisense chain: SEQ ID NO: 123: UGUAGUCUUUACCAUCCUGUU.

[1653] The sequences of the above-mentioned siRNAs are shown in the table below. It should be noted that, unless otherwise specified, the sequences in this application are presented from the 5'-3' direction. Furthermore, the meanings of the various modification symbols in this application are as follows: * indicates thiolation of the phosphate backbone (also known as thiolation), + indicates locked nucleic acid modification, and m indicates 2'-O-MOE modification.

[1654] Table 1:

[1655] (Note: When the sequence ends with TT in the above table, TT represents dTdT modification. To facilitate the preparation of sequence tables, it is abbreviated as TT).

[1656] More preferably, the ASO includes one or more of A-miR21, A-miR-10a, A-miR-30c and AmiR1306, and the miRNA includes one or more of miR-34, miR-542, miR-126 and miR-122.

[1657] More preferably, A-miR21 is selected from any one of the following: i) GATAAGCT, all of which are thiolated modifications or locked nucleic acid modifications; ii) SEQ ID NO: 124: GTCAACATCAGTCTGATAAGCTA; iii) SEQ ID NO: 125: TCAACATCAGTCTGATAAGCTA; iv) T in i) or ii) is replaced by U (i.e., GAUAAGCU, SEQ ID NO: 344: GUCAACAUCAGUCUGAUAAGCUA or SEQ ID NO: 345: UCAACAUCAGUCUGAUAAGCUA).

[1658] More preferably, A-miR-10a is ACAGGGTA, all of which are locked nucleic acid modifications.

[1659] More preferably, A-miR-30c is SEQ ID NO: 126: GCTGAGAGTGTAGGATGTTTACA.

[1660] More preferably, the sequence of miR-34 is: TGTGACAAG.

[1661] More preferably, the sequence of miR-542 is: TGGCAGTGT.

[1662] More preferably, the sequence of miR-126 is: UCGUACC, or UCGUACCG; the ribose of each nucleotide has a 2'-O-MOE modification, or CGTACCG or GTCGTT.

[1663] More preferably, the sequence of miR-122 is: GGAAGTGT.

[1664] More preferably, the sequence of AmiR1306 is: SEQ ID NO: 127: CATCACCACCAGAGCCAACGTC.

[1665] The sequences and modifications of the above miRNAs are shown in the table below.

[1666] Table 2:

[1667] In the present application, nucleic acid aptamers include nucleic acid aptamers in the form of DNA or nucleic acid aptamers in the form of RNA. The length of any nucleic acid aptamer listed in the present application is not particularly limited and can be set to 8-150nt as needed, such as aptamers of any length range such as 10-100nt, 15-95nt, 18-90nt, 20-88nt, 25-85nt, 25-80nt, 25-75nt, 25-70nt, 25-65nt, 25-60nt, 25-55nt, 25-50nt, 25-45nt, 25-40nt.

[1668] In some embodiments, the DNA-based nucleic acid aptamers include aptamers with sequences shown in the table below, or sequences with at least 85% (e.g., at least 90%, at least 95%, or at least 99%) identity to the sequences shown.

[1669] As used herein, nucleic acid aptamers refer to nucleic acid molecules (DNA or RNA) that have binding activity to specific target molecules (e.g., CD40 or PD-L1). Aptamers can bind to specific target molecules, thereby inhibiting the activity of target molecules by, for example, blocking the target molecule from binding to a cognate ligand, causing a conformational change in the target molecule, and / or blocking the active center of the target molecule. The nucleic acid aptamers of the present application can be in linear or circular form, can be RNA or DNA (e.g., single-stranded DNA), or can be modified nucleic acids or mixtures thereof.

[1670] SEQ ID NO:134: GGCAGGAAGACAAACAAGCTTGGCGGCGGGAAGGTGTTTAAATTCCCGGGTCTGCGTGGTCTGTGGTGCTGT

[1671] Table 3:

[1672] Nucleic acid aptamers in RNA form include aptamers with the sequences shown in the table below, or sequences with at least 85% (such as at least 90%, at least 95%, or at least 99%) identity to the sequences shown.

[1673] Table 4:

[1674] In certain preferred embodiments, nucleic acid drugs contain only targeting small molecule compounds, while in other preferred embodiments, they contain only targeting aptamers. Still other embodiments contain both targeting aptamers and small molecule compounds. Specific targeting small molecule compounds include, but are not limited to, one or more of folic acid, biotin, vitamin B12, and mannose. The targeting small molecule compound is located at the 5' or 3' end of at least one of sequence a, sequence b, and sequence c. In the case of biotin or folic acid, their role is to impart targeting properties to nucleic acid nanoparticles, such as specific targeting of cancer cells. Malignant tumor tissues require a high level of vitamin B12, and its related receptor (transcobalamin II receptor, CD320) is overexpressed in many cancer cells. Therefore, vitamin B12 is a highly suitable mediator for in vivo tumor diagnosis and treatment. Coupling vitamin B12 to the surface of nucleic acid nanoparticles is a practical approach to achieve safety and improve efficiency, including in imaging and therapeutic applications. Mannose itself has the effect of inhibiting cancer cell proliferation.

[1675] It should be noted that various different oligonucleotide effector molecules, depending on factors such as single-stranded or double-stranded, sequence length, secondary structure, etc., are independently mounted on the nucleic acid vector through any one or more of the following methods to improve the stability of the vector after drug loading or maintain the inherent three-dimensional conformation: 1) single-stranded bonding bridge sequence; 2) complementary sequence of the single-stranded bonding bridge sequence; 3) transition sequence, wherein the single-stranded bonding bridge sequence and transition sequence are the single-stranded bonding bridge sequence and transition sequence in the aforementioned nucleic acid vector.

[1676] The aforementioned targeting molecules and loading methods help further improve the reliability of targeted delivery of oligonucleotide effector molecules, resulting in superior specificity. They also further enhance loading stability and loading quantity. These loading methods allow for a more optimal drug size, enabling it to enter the cell membrane via cell surface receptor-mediated phagocytosis while avoiding nonspecific cell permeation and renal filtration. Consequently, a favorable particle size contributes to improved pharmacokinetics, pharmacodynamics, biodistribution, and toxicological profiles.

[1677] It should be noted that the aforementioned 1) single-stranded bridging sequence; 2) complementary sequence to the single-stranded bridging sequence; and 3) transition sequence are not required depending on the specific oligonucleotide effector molecule. For example, miRNA can also function as a transition sequence, and some RNA-based aptamers possess inherent flexibility and can be directly linked to the nucleic acid vector sequence without the need for a transition sequence or single-stranded bridging sequence.

[1678] It should be noted that, according to the actual efficacy requirements, one or more nucleotide molecules of at least one oligonucleotide effector molecule in the present application have modifications, and the modifications are selected from at least one of the following: F-type, methyl, amino, disulfide, carbonyl, carboxyl, sulfhydryl, aldehyde, thio, reverse dT and locked nucleic acid (such as AmiR-21, which has a thio-modified form or a locked nucleic acid modified form). Similarly, the phosphate backbone between the 5' end nucleotides of the antisense strand and the sense strand of the siRNA is thio-modified, and the 3' end has a dTdT modification, or the 3' end of the antisense strand of the siRNA is connected to AA, UU or a combination of any two nucleotides (including but not limited to CC, GG, CG, UG or TT). Preferably, the miRNA has a thio-modification or a locked nucleic acid modification; preferably, the nucleic acid aptamer has a thio-modification; preferably, the nucleic acid immunostimulator has a thio-modification. These modifications can improve the stability of these oligonucleotide effector molecules themselves and the stability after being mounted on the nucleic acid carrier.

[1679] Among them, phosphate backbone modification is the most basic chemical modification, among which the most commonly used backbone modification is thiolation, that is, replacing the non-bridging oxygen atom of the phosphodiester bond with a sulfur atom (PS replaces PO), which can reduce the hydrophilicity of the oligonucleotide, increase resistance to nuclease degradation, and improve stability and half-life.

[1680] In addition to modifications to the phosphate backbone, to enhance the resistance of oligonucleotide RNA to degradation by RNases, ribose modifications can sometimes be performed, primarily chemically modifying the hydroxyl groups in the ribose moiety. Ribose modifications can affect the affinity of small RNAs for target RNAs, their stability to ribozymes, and their properties after binding to RNA. Because the structures of RNA and DNA differ only by a single hydroxyl group at the 2' position, a small change in this hydroxyl group can be sufficient to elicit significant effects, dictating the conformation of the RNA sugar moiety and ultimately influencing its affinity for target RNAs. Modification of the hydroxyl group can also alter the phosphate moiety's sensitivity to nucleases, impacting the in vivo stability of oligonucleotide therapeutics. Common modifications include 2'-O-methyl, 2'-O-methoxyethyl (2'-O-MOE), and fluorine (F) substitution.

[1681] In addition, some chemical modifications target the parent ring of the ribose moiety, including LNA (locked nucleic acid), PNA (peptide nucleic acid), and PMO (phosphoroamidate morpholino oligomer). LNA is a classic nucleotide bridging modification technology that stabilizes the conformation of nucleotides by bridging the second and fourth carbon atoms, enhancing the oligonucleotide drug's resistance to nucleases and its affinity for target mRNA. PNA and PMO modifications can enhance nucleic acid drug resistance to nucleases, improve affinity, and specificity.

[1682] In different embodiments, the nucleic acid drugs of the present application are nucleic acid vectors with different sequence structures, carrying different oligonucleoside effector molecules or containing necessary small molecule compounds with targeting effects. The sequence structures of some nucleic acid drugs are shown in the table below.

[1683] Table 5:

[1684] It should be noted that, for the drugs containing siRNA in the above table, depending on the specific position in the chain and the sequence environment, in order to avoid the complementary pairing of the formed double-stranded siRNA with the connected transition sequence (including A, AA, AAA or U, UU or UUU, etc.), which affects the subsequent siRNA from exerting its biological function, on the basis of ensuring the normal biological function of the siRNA, 1-2 bases will be added or subtracted at the 5' end and / or 3' end of the sense strand or antisense strand. This means that the target sequence to be interfered with by the sense strand and antisense strand sequences forming the siRNA will not change. This deformation operation of adaptively adding or subtracting 1-2 bases at the appropriate end is easy for those skilled in the art to do.

[1685] Furthermore, the a, b, c, d, e, and f chains listed in the table above are merely lists of the individual strands used in the preparation of nucleic acid drugs and are not directly related to the a, b, and c sequences of the nucleic acid vector. In fact, in some drugs, the a, b, or c chains may represent a single a sequence (e.g., drug 98), a b sequence (e.g., drugs 2, 19, 20, and 97), or a c sequence (e.g., drugs 91-95). In other drugs, the a, b, or c chains may represent the combined length of the a, b, or c sequences and the sequence of an oligonucleotide effector molecule, potentially including a transition sequence (e.g., drugs 32 and 26). In still other drugs, the a, b, or c chains may represent the combined length of the nucleic acid sequence of an aptamer linked to the antisense strand of an siRNA via a transition sequence (e.g., drugs 31, 33, and 35). The same may be true for the remaining d, e, and f chains, or they may represent the sequence formed by linking the sense strand of an siRNA to the a, b, or c sequences. I will not elaborate on each one here. In the table above, aptamers are denoted by Apt. For example, the PD-1 aptamer is denoted by Apt PD-1. And so on. * in the table above represents thiolation modification, and + represents locked nucleic acid modification. If there are any omissions in the explanation, the sequence shall prevail.

[1686] The vector DNA3-TY used in the table above is a universal vector that uses a single-stranded linker bridge to carry different oligonucleotide effector molecules. Its specific sequence is as follows:

[1687] Table 6:

[1688] In one specific nucleic acid drug described above, CpG ODN (oligodeoxynucleotide) and CD40, AmiR-21, and AS1411 oligonucleotides are modified at the 5' ends of the three single strands of a nucleic acid vector using an oligo synthesizer in a sequence-extending manner. The resulting oligonucleotides then self-assemble into a 2CpG ODN (1826 / 2006)-CD40 aptamer-DNA vector in an assembly buffer according to the base pairing principle.

[1689] Under the mediation of CD40 aptamers, CpG ODN can actively and efficiently target and bind to B cells and pDC cells that overexpress CD40 molecules in the tumor microenvironment. CpG ODN can directly activate B cells to produce antibodies, and by stimulating and activating cell-like pDCs, induce them to secrete Th1 cytokines and pro-inflammatory cytokines, promote T cell activation, and exert an immune response effect.

[1690] When CD40 mediates the binding to CD40 on the surface of B cells and DC cells, the interaction of CD40 / CD40 signaling molecules further activates APCs (antigen presenting cells). In particular, activated DC cells act as a bridge between tumor cells and tumor-specific immune killer T cells (CTLs), and can present tumor antigens to T cells and activate T cells.

[1691] The OX40 / OXL co-stimulatory molecules in these drugs belong to the TNFR superfamily of co-stimulatory molecules and are expressed on activated Teff cells and regulatory cells (Tregs). In a weak immune response state, the OX40 aptamer binds to the OX40 receptor on activated CD4+ and CD8+ T cells, stimulating a bidirectional immune co-stimulatory effect. This promotes T cell activation, proliferation, and migration, and generates an effective, non-customized, sustained immune response. The OX40 / OXL co-stimulatory effect is particularly important for T cell survival and lifespan.

[1692] Mannose receptors (MRs) are primarily found on macrophages and dendritic cells. Mannose molecules guide the specific binding of nanonucleic acid aggregates to the MRs, which then mediate the endocytic uptake of CpG ODN-containing nanonucleic acid immune agonists. This pathway is highly efficient, selective, and saturable, increasing the presentation efficiency of mannosylated antigens and peptides by 200-10,000 times.

[1693] MUC1 mucin is overexpressed on the surface of nearly all epithelial adenocarcinoma cells, reaching levels exceeding 10-fold above normal expression. Its transmembrane and intracellular domains are highly conserved across species and exhibit a nonpolar distribution. MUC1 aptamers can be synthesized conveniently and efficiently alongside the nanoparticle nucleic acid backbone sequence using a sequence extension method. The "TTTTT" structure, acting as a "bridge" and spacer connecting the MUC1 aptamer and the nanoparticle nucleic acid, maintains the conformational structure and stability of the MUC1 aptamer, thereby enhancing the MUC1 aptamer / receptor-mediated targeting effect. MUC1 is an ideal target for active, specific tumor immunotherapy.

[1694] AmiR-21 (anti-miR-21) can specifically bind to and knock down overexpressed miR-21 in tumor cells, inhibit the activation and expansion of myeloid-derived suppressive cells MDSC (immunosuppressive effector cells) through the miR-21 / PETN / PI3K / AKt pathway, thereby suppressing the immunosuppressive tumor microenvironment; blocking or reducing the phagocytosis and absorption of miR-21 by immune cells around DGR dorsal root neurons, and alleviating cancerous and neuropathic pain caused by local inflammation.

[1695] Folate receptor...

Claims

1. A nucleic acid vector, characterized in that The nucleic acid vector comprises sequence a, sequence b and sequence c, and the nucleic acid vector is selected from a DNA vector, an RNA vector, or a DNA-RNA mixed vector; The a sequence, the b sequence and the c sequence self-assemble to form the nucleic acid vector, wherein the a sequence, the b sequence and the c sequence include a vector backbone sequence, and the vector backbone sequence includes the following core sequences: a1 sequence, b1 sequence and c1 sequence, or any variant sequence of at least one of the a1 sequence, the b1 sequence and the c1 sequence, and the variant sequence includes the insertion, deletion or substitution of at least one base; In the DNA vector, the a1 sequence is SEQ ID NO: 1, the b1 sequence is SEQ ID NO: 2, and the c1 sequence is SEQ ID NO: 3; In the RNA vector, the a1 sequence is SEQ ID NO: 4, the b1 sequence is SEQ ID NO: 5, and the c1 sequence is SEQ ID NO: 6; Wherein, the DNA-RNA hybrid vector is a vector self-assembled by combining the sequence of the DNA vector and the sequence of the RNA vector; SEQ ID NO: 1: ACGAGCGTTCCG; SEQ ID NO:2: CGGTTCGCCG; SEQ ID NO:3: CGGCCATAGCCGT; SEQ ID NO:4:ACGAGCGUUCCG; SEQ ID NO:5: CGGUUCGCCG; SEQ ID NO:6: CGGCCAUAGCCGU.

2. The nucleic acid vector according to claim 1, characterized in that The vector backbone sequence further comprises a first extension segment and an optional second extension segment, wherein the first extension segment and the second extension segment are located at the 5' end and / or the 3' end of any sequence among the a1 sequence, the b1 sequence and the c1 sequence, Preferably, the first extension segment and the second extension segment are each independently 1 to 14 nt; Preferably, the first extension segment is selected from any one or more of the following DNA extension segments or RNA extension segments corresponding to the DNA extension segment; 1) The 5' end of the a1 sequence: GACGCCC, the 3' end of the c1 sequence: GGGCGTC; 2) The 3' end of the a1 sequence: GGAGAGG, and the 5' end of the b1 sequence: CCTCTCC; 3) The 3' end of the b1 sequence: CGAGCC, and the 5' end of the c1 sequence: GGCTCG or GGCACG; 4) The 5' end of the a1 sequence: GGCGCCC or GACGCCC, and the 3' end of the c1 sequence: GGGCGCC; 5) the 3' end of the a1 sequence: GGAG, the 5' end of the b1 sequence: CTCC; 6) The 3' end of the b1 sequence: CCAGCC, and the 5' end of the c1 sequence: GGCACG or GGCTCG; Preferably, the second extension segment is selected from any one or more of the following DNA extension segments or RNA extension segments corresponding to the DNA extension segment: 1) The 5' end of the a1 sequence: C or GC, and the 3' end of the c1 sequence: GC or GCT; 2) The 3' end of the a1 sequence: AG, AGC or AGCT, and the 5' end of the b1 sequence: GCT or CT; 3) The 3' end of the b1 sequence: GC, GCG or GCGT, and the 5' end of the c1 sequence: GC or CGC; 4) the 3' end of the a1 sequence: C, AGGCC, AGGCCT or AGGAG, and the 5' end of the b1 sequence: G, GGCCT or CTCCT; 5) The 3' end of the b1 sequence is GCC or GCCT, and the 5' end of the c1 sequence is GGC.

3. The nucleic acid vector according to claim 1 or 2, characterized in that The nucleic acid vector further comprises a single-stranded bonding bridge sequence and / or a transition sequence, Wherein, the single-stranded bonding bridge sequence is selected from any one or more of the following: 1) SEQ ID NO:7:TGTAGCACGGTGGC or its complementary sequence SEQ ID NO:8:GCCACCGTGCTACA located at the 3' end of the backbone sequence of the a sequence; 2) located at the 3' end of the backbone sequence of the b sequence: SEQ ID NO: 9: TCGGCGCGGCCGTG or its complementary sequence SEQ ID NO: 10: CACGGCCGCGCCGA; 3) located at the 3' end of the backbone sequence of the c sequence: i) SEQ ID NO:11: TGCTGCTGCTGCTG or its complementary sequence SEQ ID NO:12: CAGCAGCAGCAGCA; ii) SEQ ID NO:13: CGCGGCTCGCGGCT or its complementary sequence SEQ ID NO:14: AGCCGCGAGCCGCG; Wherein, the transition sequence is a sequence formed by n consecutive U, T or A, n is a natural number of 2 to 8, preferably 3 to 6, or a sequence of random combinations of A, U, T, C and / or G, and the transition sequence is located at the 5' end or 3' end of the core sequence; Preferably, the a sequence, the b sequence and the c sequence in the nucleic acid vector are respectively as follows: The a sequence is: SEQ ID NO: 15: GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC, wherein the underlined portion is a single-stranded bridge sequence; The b sequence is: SEQ ID NO: 16: CCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, where the underlined portion is the single-stranded bridge sequence; The c sequence is: SEQ ID NO: 17: GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG, wherein the underlined portion is a single-stranded bridge sequence; or The a sequence, the b sequence and the c sequence in the nucleic acid vector are as follows: The a sequence is: SEQ ID NO: 18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC; The b sequence is: SEQ ID NO: 19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG; The c sequence is: SEQ ID NO: 20: CAGCAGCAGCAGCACGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the underlined part is the single-stranded connecting bridge sequence.

4. The nucleic acid vector according to claim 1 or 2, characterized in that The backbone sequences that self-assemble to form the nucleic acid vector are selected from any of the following groups: 1) a sequence: SEQ ID NO: 21: GCGACGCCCACGAGCGTTCCGGGAGAGGAG, b Sequence: SEQ ID NO:22: CTCCTTCCCGGTTCGCCGCGAGCCGCG, c sequence: SEQ ID NO: 23: CGCGGCACGCGGCCATAGCCGTGGGCGTCGC; 2) a sequence: SEQ ID NO: 24: GCGACGCCCACGAGCGTTCCGGGAGAGGAGCT, b sequence: SEQ ID NO: 19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG, c sequence: SEQ ID NO: 23: CGCGGCACGCGGCCATAGCCGTGGGCGTCGC; 3) a sequence: SEQ ID NO: 24: GCGACGCCCACGAGCGTTCCGGGAGAGGAGCT, b sequence: SEQ ID NO: 25: GCTCCTCTCCCGGTTCGCCGCGAGCCGCGT, c sequence: SEQ ID NO: 26: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGCT; 4) a sequence: SEQ ID NO: 24: GCGACGCCCACGAGCGTTCCGGGAGAGGAGCT, b sequence: SEQ ID NO: 25: GCTCCTCTCCCGGTTCGCCGCGAGCCGCGT, c sequence: SEQ ID NO: 27: CGCGGCACGCGGCCATAGCCGTGGGCGTCGCT; 5) a sequence: SEQ ID NO: 28: GACGCCCACGAGCGTTCCGGGAGAGG, b sequence: SEQ ID NO: 29: CCTCTCCCGGTTCGCCGCGAGCC, c sequence: SEQ ID NO: 30: GGCTCGCGGCCATAGCCGTGGGCGTC; 6) a sequence: SEQ ID NO: 18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC, b sequence: SEQ ID NO:19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG, c sequence: SEQ ID NO:31: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGC; 7) a sequence: SEQ ID NO:24: GCGACGCCCACGAGCGTTCCGGGAGAGGAGCT, b sequence: SEQ ID NO:19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG, c sequence: SEQ ID NO:26: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGCT; 8) a sequence: SEQ ID NO:24: GCGACGCCCACGAGCGTTCCGGGAGAGGAGCT, b sequence: SEQ ID NO:19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG, c sequence: SEQ ID NO:31: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGC; 9) a sequence: SEQ ID NO:24: GCGACGCCCACGAGCGTTCCGGGAGAGGAGCT, b sequence: SEQ ID NO:25: GCTCCTCTCCCGGTTCGCCGCGAGCCGCGT, c sequence: SEQ ID NO:26: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGCT; 10) a sequence: SEQ ID NO:24: GCGACGCCCACGAGCGTTCCGGGAGAGGAGCT, b sequence: SEQ ID NO:25: GCTCCTCTCCCGGTTCGCCGCGAGCCGCGT, c sequence: SEQ ID NO:31: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGC; 11) a sequence: SEQ ID NO:18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC; b sequence: SEQ ID NO:25: GCTCCTCTCCCGGTTCGCCGCGAGCCGCGT; c sequence: SEQ ID NO:26: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGCT; 12) a sequence: SEQ ID NO:32: CGACGCCCACGAGCGTTCCGGGAGAGGAGC; b sequence: SEQ ID NO:19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG; c sequence: SEQ ID NO:31: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGC; 13) Sequence a: SEQ ID NO:33: GCGGCGCCCACGAGCGTTCCGGGAGC; Sequence b: SEQ ID NO:34: GCTCCCGGTTCGCCGCCAGCCGCC; Sequence c: SEQ ID NO:35: GGCGGCAGGCGGCCATAGCCGTGGGCGCCGC; 14) Sequence a: SEQ ID NO:36: GCGGCGCCCACGAGCGTTCCGGGAGAGGCC; Sequence b: SEQ ID NO:37: GGCCTCTCCCGGTTCGCCGCCAGCCGCC; Sequence c: SEQ ID NO:38: GGCGGCTGGCGGCCATAGCCGTGGGCGCCGC; 15) Sequence a: SEQ ID NO:39: GCGGCGCCCACGAGCGTTCCGGGAGAGGCCT; Sequence b: SEQ ID NO:40: GGCCTCTCCCGGTTCGCCGCCAGCCGCCT; Sequence c: SEQ ID NO:41: GGCGGCTGGCGGCCATAGCCGTGGGCGCCGCT; 16) Sequence a: SEQ ID NO:42: GCGGCGCCCACGAGCGUUCCGGGAGAGGCC; Sequence b: SEQ ID NO:43: GGCCUCUCCCGGUUCGCCGCCAGCCGCC; Sequence c: SEQ ID NO:44: GGCGGCUGGCGGCCAUAGCCGUGGGCGCCGC; 17) Sequence a: SEQ ID NO:45: CGACGCCCACGAGCGTTCCGGGAGAGGAG; Sequence b: SEQ ID NO:46: CTCCTCTCCCGGTTCGCCGCCAGCCGCC; Sequence c: SEQ ID NO:35: GGCGGCAGGCGGCCATAGCCGTGGGCGCCGC; 18) Sequence a: SEQ ID NO:36: GCGGCGCCCACGAGCGTTCCGGGAGAGGCC; Sequence b: SEQ ID NO:43: GGCCUCUCCCGGUUCGCCGCCAGCCGCC; Sequence c: SEQ ID NO:44: GGCGGCUGGCGGCCAUAGCCGUGGGCGCCGC; 19) Sequence a: SEQ ID NO:36: GCGGCGCCCACGAGCGTTCCGGGAGAGGCC; Sequence b: SEQ ID NO:40: GGCCTCTCCCGGTTCGCCGCCAGCCGCCT; c sequence: SEQ ID NO:38: GGCGGCTGGCGGCCATAGCCGTGGGCGCCGC; 20) a sequence: SEQ ID NO:36: GCGGCGCCCACGAGCGTTCCGGGAGAGGCC; b sequence: SEQ ID NO:40: GGCCTCTCCCGGTTCGCCGCCAGCCGCCT; c sequence: SEQ ID NO:41: GGCGGCTGGCGGCCATAGCCGTGGGCGCCGCT; 21) a sequence: SEQ ID NO:36: GCGGCGCCCACGAGCGTTCCGGGAGAGGCC; b sequence: SEQ ID NO:37: GGCCTCTCCCGGTTCGCCGCCAGCCGCC; c sequence: SEQ ID NO:44: GGCGGCUGGCGGCCAUAGCCGUGGGCGCCGC; 22) a sequence: SEQ ID NO:33: GCGGCGCCCACGAGCGTTCCGGGAGC; b sequence: SEQ ID NO:46: CTCCTCTCCCGGTTCGCCGCCAGCCGCC; c sequence: SEQ ID NO:35: GGCGGCAGGCGGCCATAGCCGTGGGCGCCGC; 23) a sequence: SEQ ID NO:47: GCGGCGCCCACGAGCGTTCCGGGAGAGGAG; b sequence: SEQ ID NO:46: CTCCTCTCCCGGTTCGCCGCCAGCCGCC; c sequence: SEQ ID NO:35: GGCGGCAGGCGGCCATAGCCGTGGGCGCCGC; 24) a sequence: SEQ ID NO:48: CGCCCACGAGCGTTCCGGGAGA; b sequence: SEQ ID NO:49: TCTCCCGGTTCGCCGCGAG; c sequence: SEQ ID NO:50: CTCGCGGCCATAGCCGTGGGCG; 25) a sequence: SEQ ID NO:51: UCGCCCACGAGCGUUCCGGGAGA; b sequence: SEQ ID NO:52: UCUCCCGGUUCGCCGCGAG; c sequence: SEQ ID NO:53: UCUCGCGGCCAUAGCCGUGGGCG; 26) a sequence: SEQ ID NO:54: GCGCCCACGAGCGTTCCGGGAGAGC; b sequence: SEQ ID NO:55: CCCUGCTCTCCCGGTTCGCCGCCAGCCGCC; c sequence: SEQ ID NO: 56: GGCGGCAGGCGGCCATAGCCGTGGGCGC.

5. The nucleic acid vector according to any one of claims 1 to 4, characterized in that At least one of the base, ribose and phosphate in the a sequence, the b sequence and the c sequence has at least one modifiable site, and any of the modifiable sites has at least one of the following modifications: -F, methyl, amino, disulfide, carbonyl, carboxyl, sulfhydryl, aldehyde and thio; Preferably, part of the phosphate backbones in the a sequence, b sequence and c sequence have thio modification; Preferably, when the nucleic acid vector is an RNA vector or a DNA-RNA mixed vector, in the sequence of the RNA form in the nucleic acid vector, C and U have 2'-F modification, and A and G have 2'-OMe modification.

6. A nucleic acid drug, characterized in that: The nucleic acid drug comprises the nucleic acid vector described in any one of 1 to 5 and a bioactive substance mounted on the nucleic acid vector, wherein the bioactive substance comprises an oligonucleotide effector molecule and a targeting molecule for targeted delivery of the oligonucleotide molecule, wherein the oligonucleotide effector molecule is selected from at least one of the following: a nucleic acid immunostimulator, a nucleic acid aptamer, siRNA, miRNA and ASO; and When the oligonucleotide effector molecule includes the nucleic acid aptamer, the targeting molecule at least includes the nucleic acid aptamer; When the oligonucleotide effector molecule does not include the nucleic acid aptamer, the targeting molecule at least includes a small molecule compound with a targeting effect.

7. The nucleic acid drug according to claim 6, characterized in that: The nucleic acid immunostimulator includes one or more of CpG2006, CpG2006 variant, CpG1826, CpG2216, CpG2395, CpG-ODNT7 and CpG-BYZD; Preferably, the sequence of CpG2006 is: SEQ ID NO:57: TCGTCGTTTTGTCGTTTTGTCGTT or SEQ ID NO: 58: UCGUCGUUUUGUCGUUUUGUCGUU; Preferably, the sequence of the CpG2006 variant is: GTCGTT; Preferably, the sequence of CpG1826 is: SEQ ID NO: 59: TCCATGACGTTCCTGACG; Preferably, the sequence of CpG2216 is: SEQ ID NO:60: GGGGGACGATCGTCGGGGGG; Preferably, the sequence of CpG2395 is: SEQ ID NO:61: TCGTCGTTTTCGGCGCGCGCCG; Preferably, the sequence of the CpG-ODNT7 is: SEQ ID NO:62:TCGTCGTCGTCGTCGTCGTCG or SEQ ID NO:63:TCGTCGTCGTCGTCGTCGTCGTCG; Preferably, the sequence of the CpG-BYZD is: AGCGAA.

8. The nucleic acid drug according to claim 6, characterized in that: The siRNA includes siRNA of any one or more of the following molecules: ASAP1, ATAD2, CD24, CD47, EGFR, HBV, HSP, HS70, PD-L1, PARP-1, Survivin, TAP, TIM-3, TGF-β1 and VEGF-C; Preferably, the siRNA of ASAP1 is selected from any one of the following: i) sense strand: SEQ ID NO: 64: AUUUGCUUCCAUAAUAUCAUU, antisense strand: SEQ ID NO: 65: UGAUAUUAUGGAAGCAAAUUU; ii) sense strand: SEQ ID NO: 66: UUAGGUUUGGGGUUGGAUCUU, antisense strand: SEQ ID NO: 67: GAUCCAACCCCAAACCUAAUU; Preferably, the siRNA of ATAD2 is: the antisense strand is SEQ ID NO: 68: GCGUCGAAGUUGUAGGAUUUU, and the sense strand is: SEQ ID NO: 69: AAUCCUACAACUUCGACGCUU; Preferably, the sense strand of the siRNA for CD24 is SEQ ID NO: 70: UGUUUACAUUGUUGAGGUAUU, and the antisense strand is SEQ ID NO: 71: UACCUCAACAAUGUAAACUUU; Preferably, the siRNA of CD47 is selected from any one of the following: i) sense chain: SEQ ID NO: 72: GGUGAUUACCCAGAGAUAUTT, antisense chain: SEQ ID NO: 73: AUAUCUCUGGGUAAUCACCTT; ii) sense chain: SEQ ID NO: 74: UGGUGAAAGAGGUCAUUCCUU, antisense chain: SEQ ID NO: 75: GGAAUGACCUCUUUCACCAUU; iii) sense chain: SEQ ID NO: 76: GGAAUGACCUCUUUCACCATT, antisense chain: SEQ ID NO: 77: UGGUGAAAGAGGUCAUUCCTT; iv) sense chain: SEQ ID NO: 78: GGUGAUUACCCAGAGAUAUUU, antisense strand: SEQ ID NO:79: AUAUCUCUGGGUAAUCACCUU;_ Preferably, the siRNA of EGFR is selected from any one of the following: i) sense strand: SEQ ID NO: 80: GGCUGGUUAUGUCCUCAUUUU, antisense strand: SEQ ID NO: 81: AAUGAGGACAUAACCAGCCUU; ii) sense strand: SEQ ID NO: 82: CCUUAGCAGUCUUAUCUAAUU, antisense strand: SEQ ID NO: 83: UUAGAUAAGACUGCUAAGGUU; iii) sense strand: SEQ ID NO: 84: UGCCUUAGCAGUCUUAUCUAAUU, antisense strand: SEQ ID NO: 85: UUAGAUAAGACUGCUAAGGCAUU; iv) sense strand: SEQ ID NO: 86: UGCCUUAGCAGUCUUAUCUAAUUUU, antisense strand: SEQ ID NO: 87: AAUUAGAUAAGACUGCUAAGGCAUU; Preferably, the sense strand of the HBV siRNA is: SEQ ID NO: 88: GGACUUCUCUCAAUUUUCUUU, and the antisense strand is: SEQ ID NO: 89: AGAAAAUUGAGAGAAGUCCUU; Preferably, the sense strand of the siRNA of HSP is: SEQ ID NO:90: ​​CGCAGAACACCGUGUUCGAUU, and the antisense strand is: SEQ ID NO:91: UCGAACACGGUGUUCUGCGUU; Preferably, the sense strand of siRNA of HS70 is: SEQ ID NO:92: GGCCAACAAGAUCACCAUCUU, and the antisense strand is: SEQ ID NO:93: GAUGGUGAUCUUGUUGGCCUU; Preferably, the siRNA of PD-L1 is selected from any one of the following: i) sense strand: SEQ ID NO: 94: CCAGCACACUGAGAAUCAAUU, antisense strand: SEQ ID NO: 95: UUGAUUCUCAGUGUGCUGGUU; ii) sense strand: SEQ ID NO: 96: AGACGUAAGCAGUGUUGAATT, antisense strand: SEQ ID NO: 97: UUCAACACUGCUUACGUCUTT; Preferably, the siRNA of PARP-1 is: sense strand: SEQ ID NO:98: GAGGAAGGUAUCAACAAAUTT, antisense strand: SEQ ID NO:99: AUUUGUUGAUACCUUCCUCTT; Preferably, the siRNA of Survivin is selected from any one of the following: i) sense chain: SEQ ID NO: 100: GCAGGUUCCUUAUCUGUCACAUU, antisense chain: SEQ ID NO: 101: UGUGACAGAUAAGGAACCUGCUU; ii) sense chain: SEQ ID NO: 102: GGAAUUGGAAGGCUGGGAACCUU, antisense chain: SEQ ID NO: 103: GGUUCCCAGCCUUCCAAUUCCUU; iii) sense chain: SEQ ID NO: 104: UGCAGGUUCCUUAUCUGUCATT, antisense chain: SEQ ID NO: 105: UGACAGAUAAGGAACCUGCTT; iv) sense chain: SEQ ID NO: 106: CUGCAGGUUCCUUAUCUGUCACAUU, antisense chain: SEQ ID NO: 107: UGUGACAGAUAAGGAACCUGCAGUU; Preferably, the siRNA of TAP is selected from any one of the following: i) sense strand: SEQ ID NO: 108: GCUGCACACGGUUCAGAAUUU, antisense strand: SEQ ID NO: 109: AUUCUGAACCGUGUGCAGCUU; ii) sense strand: SEQ ID NO: 110: CAGGAUGAGUUACUUGAAAUU, antisense strand: SEQ ID NO: 111: UUUCAAGUAACUCAUCCUGUU Preferably, the sense strand of the siRNA of TIM-3 is: SEQ ID NO: 112: GUGCUCAGGACUGAUGAAATT, and the antisense strand is: SEQ ID NO: 113: UUUCAUCAGUCCUGAGCACTT; Preferably, the siRNA of TGF-β1 is selected from any one of the following: i) sense strand: SEQ ID NO: 114: GUCAACUGUGGAGCAACACUU, antisense strand: SEQ ID NO: 115: GUGUUGCUCCACAGUUGACUU; ii) sense strand: SEQ ID NO: 116: GCAACAACGCCAUCUAUGATT, antisense strand: SEQ ID NO: 117: UCAUAGAUGGCGUUGUUGCTT; Preferably, the siRNA of VEGF-C is selected from any one of the following: i) sense strand: SEQ ID NO: 118: GCAAGACGUUGUUUGAAAUUAUU, antisense strand: SEQ ID NO: 119: UAAUUUCAAACAACGUCUUGCUU; ii) sense strand: SEQ ID NO: 120: CAGCAAGACGUUGUUUGAAAUUAUU, antisense strand: SEQ ID NO: 121: UAAUUUCAAACAACGUCUUGCUGUU; iii) sense strand: SEQ ID NO: 122: CAGGAUGGUAAAGACUACAUU, antisense strand: SEQ ID NO: 123: UGUAGUCUUUACCAUCCUGUU; Preferably, the miRNA includes one or more of miR-34, miR-542, miR-126 and miR-122; Preferably, the ASO includes one or more of A-miR21, A-miR-10a, A-miR-30c and A-miR-1306; Preferably, the A-miR21 is selected from any one of the following DNA or RNA forms: i)GATAAGCT; ii) SEQ ID NO: 124: GTCAACATCAGTCTGATAAGCTA; iii) SEQ ID NO: 125: TCAACATCAGTCTGATAAGCTA; iv) T in i) or ii) is replaced by U; Preferably, the A-miR-10a is ACAGGGTA; Preferably, the A-miR-30c is SEQ ID NO: 126: GCTGAGAGTGTAGGATGTTTACA; Preferably, the sequence of miR-34 is: TGTGACAG; Preferably, the sequence of miR-542 is: TGGCAGTGT; Preferably, the sequence of miR-126 is: UCGUACC; or UCGUACCG; or CGTACCG or GTCGTT; Preferably, the sequence of miR-122 is: GGAAGTGT; Preferably, the sequence of AmiR1306 is: SEQ ID NO: 127: CATCACCACCAGAGCCAACGTC.

9. The nucleic acid drug according to claim 6, characterized in that: The nucleic acid aptamer includes a nucleic acid aptamer in the form of DNA or a nucleic acid aptamer in the form of RNA; Preferably, the nucleic acid aptamer in DNA form includes at least one of the following aptamers: A1, A15, AS1411, AFP, ATP, Act-12c, A18, BAF7-1, C-MetSL-1, CH6, CA2, CRAC Orail targets, CEA, CEA-18, CEA-T84, CSC1, CSC13, CD40, CD16a, CD19, CD3-4, CD44, CD12, CD20, CD24, CD24A-2, CD33, CD38, CD105, CD117, CD63, CD123, EGFR, EpC AM, EcR, FAP, GPC1, GPC3, GSK836, HBsAg, Her2, Her3, HMGA2, H2, IFN-γ, IL-4Ra, IL-17, LZH8, MUC1, M5, M7, M1, N5, NG-Dua, NKG2D_#-20-N-15, NSE, SARS-CoV -2-N15, SARS-CoV-2-N48, SARS-CoV-2-N58, SARS-CoV-2-N61, OX40, PSMA, PDGFRβ, PDGF, PD-L1, PD1, PTK-7, ProGRP-48, SF, TBA15, TBA29, TIMC-d, TRRA4, T FRA3, TTA1, TLS9a, TGF-βII, TNF-α, TNF, T1, Vap7, VEGF121, VEGF-V7t1, VCAM-1, VCAM-12d, PL-45, EP166, AGC, Karpas299, SW620, MDA-MB-231, MCF-7 and PC-3; The RNA-based nucleic acid aptamer comprises at least one of the following aptamers: A15, AS1411, BCMA, CTLA-4, CCL1, CEA, CD4-3, CD28, CD44, IL-4RA, EGFR, EpCAM, FGF2, FGF5, Her2, Her3, LAG-3, MUC1, MRP1, OX40, PSMA, PDGFRβ, TFRA4, TFRA3, TTA1, TIM3, TIMC-11, VEGF, VEGF165 and 4-1BB; Preferably, the nucleic acid aptamer is selected from aptamers of at least one of the following sequences: The A1 aptamer is: SEQ ID NO: 128: GGTTGCATGCCGTGGGGAGGGGGGTGGGTTTTATAGCGTACTCAG; The A15 aptamer is: SEQ ID NO: 129: CCCTCCTACATAGGG or SEQ ID NO: 130: CCCUCCUACAUAGGG; The AS1411 aptamer is: 1) SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG; or 2) SEQ ID NO: 132: GGUGGUGGUGGUUGUGGUGGUGGUGG; or 3) SEQ ID NO: 133: AUUCUGAACCGUGUGCAGCACCACGCUGCACACGGUUCAGAAUACACA; The AFP aptamer is: SEQ ID NO: 134: GGCAGGAAGACAAACAAGCTTGGCGGCGGGAAGGTGTTTAAATTCCCGGGTCT GCGTGGTCTGTGGTGCTGT; The ATP aptamer is: SEQ ID NO: 135: ACCTGGGGAGTATTGGGGAGGAAGG, or SEQ ID NO: 136: GGGAGGACGATGCGGAGGAAGGGTAGG; The Act-12c aptamer is: SEQ ID NO: 137: CGGGGAAAGTCACGGGGGGTTTCAGATGTTCTGATCGGTGTGGAG; The A18 aptamer is: SEQ ID NO: 138: CCAGATAGTCCCTGG; The BAF aptamer is: SEQ ID NO: 139: GATAACGGGCACGAATTCGGAGTG; The BCMA aptamer is: SEQ ID NO: 140: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUAC; The CTLA-4 aptamer is: 1) SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU; or 2) SEQ ID NO: 142: TCCCTACGGCGCTAACGATGGTGAAAATGGGCCTAGGGTGGACGGTGCCACCGTGCTACAAC; The C-Met-SL1 aptamer is: SEQ ID NO: 143: ATCAGGCTGGATGGTAGCTCGGTCGGGGTGGGTGGGTTGGCAAGTCTGAT; The CH6 aptamer is: SEQ ID NO: 144: AGTCTGTTGGACCGAATCCCGTGGACGCACCCTTTGGACG; The CA2 aptamer is: SEQ ID NO: 145: CCCACGTCTGCGCTTAGCTCCTGGGCCTGGATGGGC; The CCL1 aptamers are: SEQ ID NO: 146: UGACUCUCUGACAGCCUAAUUUCUCCCGAUUACCCUG; CRAC Orail target aptamers are: SEQ ID NO: 147: CCAGTAGCCATACCGGTTTGTGGATGGGGTGTATGCGAGT; The CEA aptamers are: 1) SEQ ID NO: 148: CTAGGATCCCCACTCACCATCTCTCAGCTTGCTTCCTAGC; or 2) SEQ ID NO: 149: CUAGGAUCCCCACUCACCAUCUCUCAGCUUGCUUCCUAGC; or 3) SEQ ID NO:150: TTAACTTATTCGACCATA; or 4) SEQ ID NO: 151: TCGCGCGAGTCGTCTGGGGAACCATCGAGTTACACCGACCTTCTATGTGCGGCC CCCCGCATCGTCCTCCC; The CSC1 aptamer is: SEQ ID NO: 152: ACCTTGGCTGTCGTGTTGTAGGTGGTTTGCTGCGGTGGGCTCAAGAAGAAAGC GCAAAGAGGTCAGTGGTCAGAGCGT; The CSC13 aptamer is: SEQ ID NO: 153: ACCTTGGCTGTCGTGTTGTGGGGTGTCGTATCTTTCGTGTCTTATTATTTTCTAGG TGGAGGTCAGTGGTCAGAGCGT; The CD40 aptamers are: 1) SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG; 2) SEQ ID NO: 155: AGAGACGATGCGGCCAACGAGTAGGCGATAGCGCGTGGCAGAGCGTCGCT; 3) SEQ ID NO: 156: GCCAACGAGTAGGCGATAGCGCGTGGC; The CD16a aptamers are: SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG; The CD19 aptamers are: 1) SEQ ID NO: 158: TGCGTGTGTAGTGTGTGTCGTTTCTCCTTTTTTTGGTTGCTGCTCTTAGGGATTTG GGCGG; or 2) SEQ ID NO: 159: TGCGTGTGTAGTGTGTCTGTTCTCCTTTTTTTGGTTGCTGCTCTTAGGGATTTGG GCGG, 3) SEQ ID NO: 160: UGAGCCCUGUUCGACAGGAGGCUCA; The CD4-3 aptamers are: SEQ ID NO:161: GGGAGGACGAUGCGGUUUGGGGUUUUCCCGUGCCCCAGACGACUCGCCCGA; The CD3-4 aptamers are: SEQ ID NO:162: TCTCGGACGCGTGTGGTCGGCCGAGTGGCCCACGGTAGAAGGGTTAGAACTGC TGGTTGGTGAATCTCGCTGCCTGGCCCTAGAGTG; The CD44 aptamers are: SEQ ID NO: 163: CCAAGGCCTGCAAGGGAACCAAGGACACAG; The CD12 aptamers are: SEQ ID NO: 164: GTGGATTGTTGTGTTCTGTTGGTTTTTGTGTTGTC; The CD20 aptamer is: SEQ ID NO: 165: TGCGTGTGTAGTGTGTCTGTTTTTTATCTTCTTTTATCTACTCTTAGGGATTTGGG CGG; The CD24 aptamers are: SEQ ID NO: 166: TATGTGGGTGGGTGGGCGGTTATGCTGAGTCAGCCTTGCT; The CD24A-2 aptamer is: SEQ ID NO: 167: ATCCAGAGTGACGCAGCATATGTGGGTGGGTGGGCGGTTATGCTGAGTCAGCCT TGCTTGGACACGGTGGCTTAGT; The CD28 aptamer is: SEQ ID NO: 168: GGGAGAGAGGAAGAGGGAUGGGGAUUAGACCAUAGGCUCCCAACCCCCCCC GGGAGAGAGGAAGAGGGAUGGGGAUUAGACCAUAGGCUCCCAACCCCCGGG; The CD33 aptamer is: SEQ ID NO: 169: TACCAGTGCGATGCTCAGCACGCTTATAGGGGCTGGACAAAATTCTACCCAGCC TTT; The CD38 aptamer is: SEQ ID NO: 170: TACGTGAATCTCGTACGATACTCTGTAAGCGT; The CD44 aptamer is: SEQ ID NO: 171: GGGAUGGAUCCAAGCUUACUGGCAUCUGGAUUUGCGGCGUGCCAGAAUAAAG AGUAUAACGUGUGAAUGGGAAGCUUCGAUAGGAAUUCGG; The CD105 aptamer is: SEQ ID NO: 172: GATCAGTTTTCCATGCCAGTTGGTATTCCGCGACAGTTTGATCTC; The CD117 aptamer is: SEQ ID NO: 173: GGGGCCGGGGCAAGGGGGGGGTACCGTGGTAGGAC; The CD63 aptamer is: SEQ ID NO: 174: CACCCCACCTCGCTCCCGTGACACTAATGCTA; The CD123 aptamer is: SEQ ID NO: 175: TGCGTGTGTAGTGTGTCTGGGCTACATCGATGAGCTGCCTAGGGTCCCTCTTAGG GATTTGGGCGG; The EGFR aptamers are: 1) SEQ ID NO: 176: GCCTTAGTAACGTGCTTTGATGTCGATTCGACAGGAGGC; or 2) SEQ ID NO: 177: GCCUUAGUAACGUGCUUUGAUGUCGAUUCGACAGGAGGC; or 3) SEQ ID NO: 178: UGCCGCUAUAAUGCACGGAUUUAAUCGCCGUAGAAAAGCAUGUCAAAGCCG UU; EpCAM aptamers are: 1) SEQ ID NO:179: GCGACUGGUUACCCGGUCG; or 2) SEQ ID NO: 180: CACTACAGAGGTTGCGTCTGTCCCACGTTGTCATGGGGGGTTGGCCTG; or 3) SEQ ID NO: 181: GACAAACGGGGGAAGATTTGACGTCGACGAC; The EcR aptamer is: SEQ ID NO: 182: GCAGTCCACTGCGGGGGTCTATACGTGAGGAAGAAGTGGGCAGGTC; The FGF2 aptamers are: 1) SEQ ID NO:183:GGGAUACUAGGGCAUUAAUGUUACCAGUGUAGUCCC; 2) SEQ ID NO: 184: GGGAAACUAGGGCGUUAACGUGACCAGUGUUUCUCGA; 3) SEQ ID NO: 185: GGGAAACUAGGGCGUUAACGUGACCAGUGUUUCCC; The FGF5 aptamer is: SEQ ID NO: 186: GGGCGACCUCUCCGUACUGACCUACAGAGCGACAUACUAGUGUAUCCAGAU CGCCC; The FAP aptamer is: 1) SEQ ID NO: 187: TGGGGGTTGAGGCTAAGCCGA; or 2) SEQ ID NO: 188: CCGCTCGAGCTAGTCTGACAAAGAGAAACAC; The GPC1 aptamer is: SEQ ID NO: 189: AACGGAGTGTGGCTAACTCGA; The GPC3 aptamer is: SEQ ID NO: 190: TAACGCTGACCTTAGCTGCATGGCTTTACATGTTCCA; The GSK836 aptamer is: SEQ ID NO: 191: GCAGAGGTGAAGCGAAGTCG; HBsAg aptamers are: SEQ ID NO: 192: CACAGCGAACAGCGCGGGACATAATAGTGCTTACTACGAC; The Her2 aptamers are: 1) SEQ ID NO: 193: AGCCGCGAGGGGAGGGATAGGGTAGGGCGCGGCT; or 2) SEQ ID NO: 194: AGCCGCGAGGGGAGGGAUAGGGUAGGGCGCGGCU; Her3 aptamers are: 1) SEQ ID NO: 195: GGGAGCTCAGAATAAACGCTCAAAGGGTCAAGCTGATTACACTTTGTCCACTAT TGGGTCCTTCGACATGAGGCCCGGATC; or 2) SEQ ID NO: 196: GGGAGCTCAGAATAAACGCTCAAGGCTAACAGCACGCAACGGGGGGGAGTAAT CGTGTCTGTTCGACATGAGGCCCGGATC; or 3) SEQ ID NO: 197: CAGCGAAAGUUGCGUAUGGGUCACAUCGCAGGCACAUGUCAUCUGGGCG; or 4) SEQ ID NO: 198: GAAUUCCGCGUGUGCCAGCGAAAGUUGCGUAUGGGCCACAUCGCAGGCACA UGUCAUCUGGGCGGUCCGUUCGGGAUCC; The HMGA2-aptamer is: SEQ ID NO: 199: GGAAAAAATTTTTTAAAAAACCC; The H2 aptamer is: SEQ ID NO: 200: GGGCCGTCGAACACGAGCATGGTGCGTGGACCTAGGATGACCTGAGTACTGTC C； The IFN-γ aptamer is: SEQ ID NO: 201: CCGCCCAAATCCCTAAGAGAAGACTGTAATGACATCAAACCAGACACACACAC TACACACGCA; IL-4Ra aptamer is: 1) SEQ ID NO: 202: GGAGGACGAUGCGGAAAAAGCAACAGGGUGCUCCAUGCGCAUGGAACCUGC GCGCAGACGACUCGCUGAGGAUCCGAGA; or 2) SEQ ID NO: 203: AAAAAGCACAGGGUGCUCCAUGCGCAUGGAACCUGCGCG; IL-17 Aptamer: 1) SEQ ID NO: 204: CTTGGATCACCATAGTCGCTAGTCGAGGCT; or 2)SEQ ID NO:205:GCGGCATCCTATCACGCATTGACC The LAG-3 aptamer is: SEQ ID NO: 206: GGGAGAGAGAUAUAAGGGCCUCCUGAUACCCGCUGCUAUCUGGACCGAUCC CAUUACCAAAUUCUCUCCC; The LZH8 aptamer is: SEQ ID NO: 207: ATCCAGAGTGACGCAGCATATTAGTACGGCTTAACCCCATGGTGGACACGGTGG CTTAGT; The MUC1 aptamers are: 1) SEQ ID NO: 208: GCAGTTGATCCTTTGGATACCCTGG; or 2) SEQ ID NO: 209: GAAGTGAAAATGACAGAACACAACA; or 3) SEQ ID NO: 210: AACCGCCCAAATCTCTAAGAGTCGGACTGCAACCTATGCTATCGTTGATGTCTGT CCAAGCAACACAGACACACTACACACACGCACA; or 4) SEQ ID NO: 211: AATGACAGAACACAACATT; or 5) SEQ ID NO: 212: GCAGUUGAUCCUUUGGAUACCCUGG; The M5 aptamer is: SEQ ID NO: 213: AGCAGCACAGAGGTCAGATGCTTGGTTCCACCGTACTGACTGTAGTAAAATCTG ATCACTCCTATGCGTGCTACCGTGAA; The M7 aptamer is: SEQ ID NO: 214: AGCAGCACAGAGGTCAGATGTAGTCGGTCTTCTTGTTTGAAACTGCTAATTTTG AAAAAACCTATGCGTGCTACCGTGAA; The M1 aptamer is: SEQ ID NO: 215: AGCAGCACAGAGGTCAGATGATATAACCTTAATAAATAAAATATAAATTATTTAAT CTTATCGTCGTGCTACCGTGAA; The MRP1 aptamer is: SEQ ID NO: 216: GGGAGAUAGUCAACAAAUCGUUUGGGGCGACUUCUCCUUCCUCCC. N5 fragment:SEQ ID NO:217: GATTGAGTAGATAGTGGTTCTGTACGTAGTGAAAGAGTGG. NG-Two-Dragon:SEQ ID NO:218: CAAGTTGCTCGTCGCGATACGTTTGGTTGGTGTGGTTGGCAGTATCGCAGGTCC AAGTTGCTCGTCGCGATACAACGGAGTGTGGCTAACTCGA. NKG2D_#-20-N-15 fragment:SEQ ID NO:219: CAAGTTGCTCGTCGCGATACGTTTGGTTGGTGTGGTTGGCAGTATC; NSE1:SEQ ID NO:220: TCACACGGACCTCTCTCTACATTAATTGCGCATTTCGTT. SARS-CoV-2-N15 fragment:SEQ ID NO:221: GCTGGATGTTCATGCTGGCAAAATTCCTTAGGGGCACCGTTACTTTGACACATCC AGC SARS-CoV-2-N48 fragment:SEQ ID NO:222: GCTGGATGTCGCTTACGACAATATTCCTTAGGGGCACCGCTACATTGACACATCC AGC SARS-CoV-2-N58 fragment:SEQ ID NO:223: GCTGGATGTCACCGGATTGTCGGACATCGGATTGTCTGAGTCATATGACACATCC AGC SARS-CoV-2-N61 fragment:SEQ ID NO:224: GCTGGATGTTGACCTTTACAGATCGGATTCTGTGGGGCGTTAAACTGACACATC CAGC OX40 license plate: 1)SEQ ID NO:225: GGGAGGACGATGCGGCAGTCTGCATCGTAGGAATCGCCACCGTATACTTTCCCA CCAGACGACTCGCTGAGGATCCGAGA. 2)SEQ ID NO:226: GGGAGGACGAUGCGGCAGUCUGCAUCGUAGGAAUCGCCACCGUAUACUUUC CCACCAGACGACUCGCUGAGGAUCCGAGA. 3) SEQ ID NO: 227: CAGTCTGCATCGTAGGATTAGCCACCGUATCTTTCCCAC; 4) SEQ ID NO: 228: GGGAGGACGAUGCGGCAGUCUGCAUCGUAGGAAUCGCCACCGUAUACUUUC CCACCAGACGACUCGCUG; 5) SEQ ID NO: 229: CAGUCUGCAUCGUAGGAAUCGCCACCGUAUACUUUCCCAC; 6) SEQ ID NO: 230: GGGAUGCGGAAAAAAGAACACUUCCGAUUAGGGCCCACCCUAACGGCCGCA GAC; PSMA aptamers are: 1) SEQ ID NO: 231: GGGAGGACGATGCGGATCAGCCATGTTTACGTCACTCCT; or 2) SEQ ID NO: 232: GCGTTTTCGCTTTTGCGTTTTGGGTCATCTGCTTACGATAGCAATGCT; or 3) SEQ ID NO: 233: GGGAGGACGAUGCGGAUCAGCCAUGUUUACGUCACUCCU; or 4) SEQ ID NO: 234: GGGACCGAAAAAGACCUGACUUCUAUACUAAGUCUACGUUCCC; The PDGFRβ aptamers are: 1) SEQ ID NO: 235: TGTCGTGGGGCATCGAGTAAATGCAATTCGACA; or 2) SEQ ID NO: 236: UGUCGUGGGGCAUCGAGUAAAUGCAAUUCGACA; The PDGF aptamers are: SEQ ID NO:237: CAGGCTACGGCACGTAGAGCATCACCATGATCCTG; The aptamer of PD-L1 is selected from any one or more of the following: 1) SEQ ID NO: 238: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGG; 2) SEQ ID NO: 239: GCCCCAGTTAGCTTTCCCCCTCTTGTCTCTTTG; 3) SEQ ID NO: 240: ATCGCCCGCAGCACCCATTTGTTTTTTTTTG; 4) SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT; 5) SEQ ID NO: 242: TGCCCGCACATCAACTCATTGATAGACAATGCGTCCACTCGGGCA; 6) SEQ ID NO:243: TGCCCGCACATCAACTCATTGATAGACAATGCGTCCACTACGGGC; 7) SEQ ID NO:244: CGGGCACACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT; 8) SEQ ID NO:245: GTTGGTCACATCAACTCATTGATAGACAATGCGTCCACTACCAAC; 9) SEQ ID NO:246: GGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCC; 10) SEQ ID NO:247: TGGTTGCACATCAACTCATTGATAGACAATGCGTCCACTCAACCA; 11) SEQ ID NO:248: TACAGGTTCTGGGGGGTGGGTGGGGAACCTGTT; 12) SEQ ID NO:249: CTACGAGACGAACTTATGCGTAATAATGACTGTCGTAG; The PD1 aptamer is selected from any one or more of the following: 1) SEQ ID NO:250: GACGATAGCGGTGACGGCACAGACGGTACAGTTCCCGTCCCTGCACTACACGTA TGCCGCTTCCGTCCGTCGCTC; 2) SEQ ID NO:251: GAGCGACGGACGGAAGCGGCATACGTGTAGTGCAGGGACGGGAACTGTACCGT CTGTGCCGTCACCGCTATCGTC; 3) SEQ ID NO:252: GGATCCTATGACGCATTGACCCGCTGCCTCTACTGAGGCTGTGTCAGTGTGCGG CTCGGACTGTTGAATTC; 4) SEQ ID NO:253: AGCGGTGACGGCACAGACGGTACAGTTCCCGTCCCTGCACTACACGTATGCCGC T； 5) SEQ ID NO:254: ACCGACAGTGAAGGACTCAGCGAACTCTCAGACTCGGTTC; The PTK-7 aptamer is: SEQ ID NO:255: ATCTAACTGCTGCGCCGCCGGGAAAATACTGTACGGTTAGA; The ProGRP-48 aptamer is: SEQ ID NO:256: CATGCGGAGTAGAGCGAGCCCAGATAGTCCCTGGTTATTTCCTTAGG; The SF aptamer is: SEQ ID NO:257: GATCTCTCTCTGCCCTAAGTCCGCACCCGTGCTTCCCTGT; The TBA15 aptamer is: SEQ ID NO:258: GGTTGGTGTGGTTGG; The TBA29 aptamer is: SEQ ID NO:259: AGTCCGTGGTAGGGCAGGTTGGGGTGACT; The TFRA4 aptamer is: SEQ ID NO:260: GCGTGGTACCACGC or SEQ ID NO:261: GCGUGGUACCACGC; The TFRA3 aptamer is: 1) SEQ ID NO:262: GCGTGGTCACACGC; or 2) SEQ ID NO:263: GCGUGGUCACACGC; or 3) SEQ ID NO:264: GCGGCGCCCACGAGCGTTCGCGTGGTCACACGCGTTCCGCCCTCCTACATAGGG CGCATAGCCGTGGGCGCCGC; The TTA1 aptamer is: SEQ ID NO:265: CCTGCACTTGGCTTGGATTTCAGAAGGGAGACCC; or SEQ ID NO:266: CTGCACTTGGCTTGGATTTCAGAAGGGAGACCC; or SEQ ID NO:267: CCUGCACUUGGCTTGGAUUUCAGAAGGGAGACCC; The TLS9a aptamer is: SEQ ID NO:268: AGTCCATTTTATTCCTGAATATTTGTTAACCTCATGGAC; The TGF-β aptamer is: SEQ ID NO:269: ACATTGCTGCGTGATCGCCTCACATGGGTTTGTCTGGTCGATTTGGAGGTGGTG GGTGGC; The TIM3 aptamer is: SEQ ID NO:270: GGGAGAGGACCAGUAGCCACUAUGGUGUUGGAGCUAGCGGCAGAGCGUCGC GGUCCCUCCC; or SEQ ID NO:271: GGGAGAGGACCAGUACUGGUAGUUCUCUGUGCGACUCCUACAGAGCGUCGC GGUCCCUCCC; The TIMC-d aptamer is: SEQ ID NO:272: AAGCAACACUUAGUCGCGAUUGAUACGUGCGCAGUCAU; The TIMC-11 aptamer is: SEQ ID NO:273: GGAGGACGAUGCGGGGAAGCAACACUUAGUCGCGAUUGAUACGUGCGCAGU CAUCAGACGACUCGCUGAGGAUCCGAGA; The TNF-α aptamer is: SEQ ID NO: 274: GCGGCCGATAAGGTCTTTCCAAGCGAACGAAAA; The TNF aptamer is: SEQ ID NO: 275: GCGCCACTACAGGGGAGCTGCCATTCGAATAGGTGGGCCGC; The T1 aptamer is: SEQ ID NO: 276: CGCTCGATAGATCGAGCTTCGCTCGATGTGGTGTTGTGGGGGCTTGTATTGGTCG ATCACGCTCTAGAGCACTG; The sequence of the Vap7 aptamer is: SEQ ID NO: 277: TGGTGGGGGTGGACGGGCCGGGTAGA; The VEGF aptamers are: SEQ ID NO: 278: AUGCAGUUUGAGAAGUCGCGCAU; or SEQ ID NO: 279: GGTGGGGGTGGACGGGCCGGGTAGA; The VEGF165 aptamer is: SEQ ID NO: 280: CGGAAUCAGUGAAUGCUUAUACAUCCG; The VEGF121 aptamer is: SEQ ID NO: 281: TGTGGGGGTGGACTGGGTGGGTACC; The VEGF-V7t1 aptamer is: SEQ ID NO: 282: TGTGGGGGTGGACGGGCCGGGTAGA; The VCAM-1 aptamer is: SEQ ID NO: 283: ATACCAGCTTATTCAATTGGACACGGCAAAGGGGTATAGCCTACCGGACCGTGA ACATGGAATGGTGTGCTGCGTGGAGATAGTAAGTGCAATCT; or SEQ ID NO:284: GGACACGGCAAAGGGGTATAGCCTACCGGACCGTGAACATGGAATGGTGTGCT GCGTGG; The VCAM-12d aptamer is: SEQ ID NO: 285: AGGGAATCTTGCCTAGGGAGGGAGTAGCGAAAGGGCTCA; The 4-1BB aptamer is: SEQ ID NO: 286: GGGAGAGAGGAAGAGGGAUGGGCGACCGAACGUGCCCUUCAAAGCCGUUCA CUAACCAGUGGCAUAACCCAGAGGUCGAUAGUACUGGAUCCCCCC; The PL-45 aptamer is: SEQ ID NO: 287: ACTCATAGGGTTAGGGGCTGCTGGCCAGATACTCAGATGGTAGGGTTACTATGA GC; The EP166 aptamer is: SEQ ID NO: 288: AACAGAGGGACAAACGGGGGAAGATTTGACGTCGACGACA; The AGC aptamer is: SEQ ID NO: 289: CGACCCGGCACAAACCCAGAACCATATACACGATCATTAGTCTCCTGGGCCG; The Karpas299 aptamer is: SEQ ID NO: 290: ATCCAGAGTGACGCAGCACCACCACCGTACAATTTTTTTCATTACCTACTCGGC; The SW620 aptamer is: SEQ ID NO: 291: CCCATCAATGTTACGACCCGCTAGGGCTGCTGTGCCATCGGGTAA; The MDA-MB-231 aptamer is: SEQ ID NO: 292: AGAATTCAGTCGGACAGCGAAGTAGTTTTCCTTCTAACCTAAGAACCCGCGGCA GTTTAATGTAGATGGACGAA; The MCF-7 aptamer is: SEQ ID NO: 293: GCATGGGGTTTCGGCGTTTCGTTCTATCTTGTTTCTGTTAGCGTCT; The PC-3 aptamer is: SEQ ID NO: 294: TGCCACTACAGCTGGTTCGGTTTTGGTGACTTCGTTCTTCGTTGTGGTGCTTAGTG GC.

10. The nucleic acid drug according to claim 6, characterized in that: The small molecule compound with targeting effect is selected from one or more of folic acid, biotin, vitamin B12 and mannose, and is located at the 5' end or 3' end of at least one of the a sequence, the b sequence and the c sequence.

11. The nucleic acid drug according to any one of claims 6 to 10, characterized in that: The various oligonucleotide effector molecules are independently mounted on the nucleic acid vector by any one or more of the following methods: 1) a single-stranded bonding bridge sequence; 2) a complementary sequence of the single-stranded bonding bridge sequence; 3) a transition sequence, wherein the single-stranded bonding bridge sequence and the transition sequence are the single-stranded bonding bridge sequence and the transition sequence in the nucleic acid vector according to claim 3; Preferably, at least one of the oligonucleotide effector molecules has a modification on one or more nucleotide molecules, and the modification is selected from at least one of the following: F-generation, methyl, amino, disulfide, carbonyl, carboxyl, sulfhydryl, aldehyde, thio, reverse dT and locked nucleic acid; Preferably, the phosphate backbone between the 5'-end nucleotides of the antisense strand and the sense strand of the siRNA is thio-modified, and the 3'-end has a dTdT modification or UU, or the 3'-end of the antisense strand of the siRNA is connected with AA, UU or a combination of any two nucleotides; Preferably, the miRNA has a thiolation modification or a locked nucleic acid modification; Preferably, the nucleic acid aptamer has any one or more of the following modifications: thio, 2'-F or 2'-O-MOE; Preferably, the nucleic acid immunostimulator has a thiolation modification.

12. The nucleic acid drug according to claim 11, characterized in that: The nucleic acid drug is selected from any one of the following: Drug 1): 3*CpG2006-DNA vector, wherein, The DNA vector is the 13th group of the nucleic acid vector according to claim 4, wherein the three CpG2006 are connected to the 5' ends of the a sequence, the b sequence and the c sequence respectively through the transition sequence; Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the transition sequence is TTTTT; Drug 2): 2*CpG1826-2*mannose-DNA vector, wherein the DNA vector is the group 1) in the nucleic acid vector according to claim 4, the two CpG1826 are connected to the 5' end of the a sequence and the c sequence respectively through the transition sequence, and the two mannose are located at the 5' end and 3' end of the b sequence respectively; Preferably, the transition sequence is TTTTT; Preferably, the sequence of CpG1826 is: SEQ ID NO: 59: TCCATGACGTTCCTGACG, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Drug 3): 2*CpG1826-CD40 aptamer-DNA vector, wherein the DNA vector is the group 1) in the nucleic acid vector according to claim 4, the two CpG1826s are connected to the 5' end of the a sequence and the c sequence respectively through the transition sequence, and the CD40 aptamer is connected to the 5' end of the b sequence through the transition sequence; Preferably, the sequence of CpG1826 is: SEQ ID NO: 59: TCCATGACGTTCCTGACG, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the transition sequence is TTTTT; Preferably, the sequence of the CD40 aptamer is SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG; Drug 4): 2*CpG2006-CD40 aptamer-DNA vector, wherein the DNA vector is the group 1) in the nucleic acid vector according to claim 4, the two CpG2006s are connected to the 5' end of the a sequence and the c sequence respectively through the transition sequence, and the CD40 aptamer is connected to the 5' end of the b sequence through the transition sequence; Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the transition sequence is TTTTT; Preferably, the sequence of the CD40 aptamer is SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG; Drug 5): 4*CpG2006-CD40 aptamer-DNA vector, wherein the DNA vector is the group 1) in the nucleic acid vector according to claim 4, two CpG2006s are connected in series to form a CpG2006 doublet, the two CpG2006 doublets are connected to the 5' end of the a sequence and the c sequence respectively, and the CD40 aptamer is connected to the 5' end of the b sequence through the transition sequence; Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the transition sequence is TTTTT; Preferably, the sequence of the CD40 aptamer is SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG; Drug 6): 2*CpG1826-CD40 aptamer-2*mannose-DNA vector, wherein the DNA vector is the group 1) in the nucleic acid vector according to claim 4, the two CpG1826s are connected to the 5' end of the a sequence and the c sequence respectively through the transition sequence, the CD40 aptamer is connected to the 5' end of the b sequence through the transition sequence, and the two mannoses are located at the 3' end of the b sequence and the c sequence respectively; Preferably, the sequence of CpG1826 is: SEQ ID NO: 59: TCCATGACGTTCCTGACG, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the transition sequence is TTTTT; Preferably, the sequence of the CD40 aptamer is SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, and the phosphate backbone between the first 3 nucleotides at the 5' end is thiolated; Drug 7): CpG1826-CD40 aptamer-mannose-MUC1 aptamer-DNA vector, wherein the DNA vector is the group 1) in the nucleic acid vector according to claim 4, the CpG1826 is connected to the 5' end of the a sequence through the transition sequence, the CD40 aptamer is connected to the 5' end of the b sequence through the transition sequence, the MUC1 aptamer is connected to the 5' end of the c sequence through the transition sequence, and the mannose is located at the 3' end of the c sequence; Preferably, the sequence of CpG1826 is: SEQ ID NO: 59: TCCATGACGTTCCTGACG, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the transition sequence is TTTTT; Preferably, the sequence of the CD40 aptamer is SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG; Preferably, the MUC1 aptamer sequence is: SEQ ID NO: 208: GCAGTTGATCCTTTGGATACCCTGG; Drug 8) 2*CpG2006-CD40 aptamer-AmiR-21-3*mannose-DNA vector, wherein the DNA vector is the first group of the nucleic acid vector according to claim 4, the two CpG2006s are connected to the 5' ends of the a sequence and the c sequence respectively through the transition sequence, the CD40 aptamer is connected to the 5' end of the b sequence through the transition sequence, the AmiR-21 is directly connected to the 3' end of the b sequence, and the three mannoses are connected to the 3' ends of the a sequence, the AmiR-21 and the c sequence respectively; Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the transition sequence is TTTTT; Preferably, the sequence of the CD40 aptamer is SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG; Preferably, the sequence of AmiR-21 is GATAAGCT, wherein each nucleotide is modified with a locked nucleic acid; Drug 9): 2*CpG2006-CD40 aptamer-CD16a aptamer-CTLA-4 aptamer-DNA vector, wherein the DNA vector is the second group of the nucleic acid vector according to claim 4, the two CpG2006s are connected to the 5' end of the a sequence and the c sequence respectively through the transition sequence, the CD40 aptamer is connected to the 3' end of the b sequence through the transition sequence, the CD16a aptamer is connected to the 5' end of the b sequence through the transition sequence, and the CTLA-4 aptamer is connected to the 3' end of the c sequence through the transition sequence; Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the transition sequence is TTTTT; Preferably, the sequence of the CD16a aptamer is: SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, with thiolation modification between the first two positions of the 5' end; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the phosphate backbone between the last two nucleotides at the 3' end is thiolated; Preferably, the sequence of the CTLA-4 aptamer is: SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU, a thiolation modification exists in the phosphate backbone between the 2nd and 3rd nucleotides from the 3' end; Drug 10): 2*CpG2006-CTLA-4 aptamer-PD-L1 aptamer-DNA vector, wherein, The DNA vector is the third group of the nucleic acid vector according to claim 4, wherein two CpG2006 are connected in series to form a CpG2006 doublet, the CpG2006 doublet is connected to the 5' end of the a sequence through the transition sequence, the PD-L1 aptamer is connected to the 5' end of the c sequence through the transition sequence, and the CTLA-4 aptamer is connected to the 5' end of the b sequence through the transition sequence; Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, and the phosphate backbone between the first two nucleotides at the 5' end is thiolated; Preferably, the sequence of the CTLA-4 aptamer is: SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU, and the phosphate backbone between the first two nucleotides at the 5' end is thiolated; Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the transition sequence is TTTTT; Drug 11): CpG2006-CD40 aptamer-PD-L1 aptamer-DNA vector, selected from any of the following structures: i) CCPD3: The DNA vector is group 12) of the nucleic acid vector according to claim 4, wherein the CpG2006 is connected to the 5' end of the a sequence through the transition sequence, the PD-L1 aptamer is connected to the 5' end of the c sequence through the transition sequence, and the CD40 aptamer is connected to the 5' end of the b sequence through the transition sequence; wherein, In the DNA vector, the phosphate backbone between the 3' end of the a sequence, the 3' end of the b sequence and the first 3 nucleotides of the 3' end of the c sequence is thiolated; Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, and the phosphate backbone between the first 3 adjacent nucleotides at the 5' end is thiolated; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, wherein the phosphate backbone between the first three adjacent nucleotides at the 5' end is thiolated; Preferably, the transition sequence is TTTTT; or ii) CCPD3 variant 1: The DNA vector is the group 12) of the nucleic acid vector according to claim 4, wherein the CpG2006 is connected to the 5' end of the a sequence via the transition sequence TTTTT, the CD40 aptamer is connected to the 5' end of the b sequence via the transition sequence TTTTT; the PD-L1 aptamer is connected to the 5' end of the c sequence via the transition sequence ATTT, wherein: In the DNA vector, the phosphate backbone between the 3' end of the a sequence, the 3' end of the b sequence and the first two nucleotides of the 3' end of the c sequence is thiolated; Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, wherein the phosphate backbone between the first three adjacent nucleotides at the 5' end is thiolated; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 238: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGG, and the phosphate backbone between the first 4 adjacent nucleotides at the 5' end is thiolated; or iii) CCPD3 variant 2: The sequence of the DNA vector is: a Sequence: SEQ ID NO: 295: GCCCACGAGCGTTCCGGGAGA; b sequence: SEQ ID NO:49:TCTCCCGGTTCGCCGCGAG; c sequence: SEQ ID NO: 296: CTCGCGGCCATAGCCGTGGGC; The CpG2006 is connected to the 5' end of the a sequence via the transition sequence TTTT, the CD40 aptamer is connected to the 5' end of the b sequence via the transition sequence TTTT, and the PD-L1 aptamer is connected to the 5' end of the c sequence via the transition sequence TTTT. Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 156: GCCAACGAGTAGGCGATAGCGCGTGGC, wherein the phosphate backbone between the first 4 adjacent nucleotides at the 5' end is thiolated; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, and the phosphate backbone between the first 5 adjacent nucleotides at the 5' end is thiolated; or iv) CCPD3 variant 3: The sequence of the DNA vector is: a Sequence: SEQ ID NO: 295: GCCCACGAGCGTTCCGGGAGA; b sequence: SEQ ID NO:49:TCTCCCGGTTCGCCGCGAG; c sequence: SEQ ID NO: 296: CTCGCGGCCATAGCCGTGGGC; The CpG2006 is connected to the 5' end of the a sequence via the transition sequence TTTT, the CD40 aptamer is connected to the 5' end of the b sequence via the transition sequence TTTT; the PD-L1 aptamer is connected to the 5' end of the c sequence via the transition sequence TTTT. Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 156: GCCAACGAGTAGGCGATAGCGCGTGGC, wherein the phosphate backbone between the first 4 adjacent nucleotides at the 5' end is thiolated; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 246: GGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCC, and the phosphate backbone between the first 4 adjacent nucleotides at the 5' end is thiolated; v) CCPD3 variant 4: The sequence of the DNA vector is: a Sequence: SEQ ID NO: 295: GCCCACGAGCGTTCCGGGAGA; b sequence: SEQ ID NO:49:TCTCCCGGTTCGCCGCGAG; c sequence: SEQ ID NO: 296: CTCGCGGCCATAGCCGTGGGC; The CpG2006 is connected to the 5' end of the a sequence via the transition sequence TTTT, the CD40 aptamer is connected to the 5' end of the b sequence via the transition sequence TTTT; the PD-L1 aptamer is connected to the 5' end of the c sequence via the transition sequence TTTT. Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 156: GCCAACGAGTAGGCGATAGCGCGTGGC, wherein the phosphate backbone between the first 4 adjacent nucleotides at the 5' end is thiolated; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 248: TACAGGTTCTGGGGGGTGGGTGGGGAACCTGTT, and the phosphate backbone between the first 4 adjacent nucleotides at the 5' end is thiolated; vi) CCPD3 variant 5: The sequence of the DNA vector is: a Sequence: SEQ ID NO: 18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC; b Sequence: SEQ ID NO: 19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG; c sequence: SEQ ID NO: 20: CAGCAGCAGCAGCACGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, wherein SEQ ID NO: 12: CAGCAGCAGCAGCA is a single-stranded connecting bridge sequence; The CpG2006 is connected to the 5' end of the a sequence via the transition sequence TTTT, the CD40 aptamer is connected to the 5' end of the b sequence via the transition sequence TTTTT, and the PD-L1 aptamer is connected to the 5' end of the b sequence via the transition sequence TTTTT is connected to the 3' end of the complementary sequence of the single-stranded bridge sequence, and is connected to the 5' end of the c sequence through the complementary pairing between the single-stranded bridge sequence and its complementary sequence; Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, wherein the phosphate backbone between the first 5 adjacent nucleotides at the 5' end is thiolated; Preferably, the complementary sequence of the single-stranded connecting bridge sequence - the sequence of the PD-L1 aptamer is: SEQ ID NO: 297: TGCTGCTGCTGCTGTTTTTACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, and the phosphate backbone between the first 4 adjacent nucleotides at the 3' end is thiolated, wherein, SEQ ID NO:11: TGCTGCTGCTGCTG is the complementary sequence of the single-stranded connecting bridge sequence; vii) CCPD3 variant 6: The sequence of the DNA vector is: a Sequence: SEQ ID NO: 18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC; b Sequence: SEQ ID NO: 19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG; c sequence: SEQ ID NO: 20: CAGCAGCAGCAGCACGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, among which, SEQ ID NO: 12: CAGCAGCAGCAGCA is a single-stranded connecting bridge sequence; The CpG2006 is connected to the 5' end of the a sequence through the transition sequence TTTT, the CD40 aptamer is connected to the 5' end of the b sequence through the transition sequence TTTTT, the PD-L1 aptamer is connected to the 3' end of the complementary sequence of the single-stranded bridge sequence through the transition sequence TTTTT, and is connected to the 5' end of the c sequence through the complementary pairing of the single-stranded bridge sequence and its complementary sequence; Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, wherein the phosphate backbone between the first 5 adjacent nucleotides at the 5' end is thiolated; Preferably, the complementary sequence of the single-stranded connecting bridge sequence -TTTTT-the sequence of the PD-L1 aptamer is: SEQ ID NO: 298: TGCTGCTGCTGCTGTTTTTTACAGGTTCTGGGGGGTGGGTGGGGAACCTGTT, the phosphate backbone between the first 4 adjacent nucleotides at the 3' end is thiolated, among which, SEQ ID NO:11: TGCTGCTGCTGCTG is the complementary sequence of the single-stranded connecting bridge sequence; viii) CCPD3 variant 7: The sequence of the DNA vector is: a sequence: SEQ ID NO: 15: GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC, wherein, SEQ ID NO:7: TGTAGCACGGTGGC is the single-stranded connecting bridge sequence A; b sequence: SEQ ID NO: 16: CCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, wherein SEQ ID NO: 9: TCGGCGCGGCCGTG is the single-stranded connecting bridge sequence B; c sequence: SEQ ID NO: 17: GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG, wherein, SEQ ID NO: 11: TGCTGCTGCTGCTG is a single-stranded connecting bridge sequence C; The CpG2006 is connected to the 5' end of the complementary sequence C' of the single-stranded bridge C sequence through a transition sequence, and the CpG2006 is connected to the 3' end of the c sequence through complementary pairing between the complementary sequence C' and the single-stranded bridge C sequence; The PD-L1 aptamer is sequentially connected to the transition sequence and the complementary sequence B' of the single-stranded bridge sequence B. The PD-L1 aptamer is connected to the 3' end of the b sequence through the complementary pairing of the complementary sequence B' and the single-stranded bridge sequence B. The CD40 aptamer is sequentially connected to the transition sequence and the complementary sequence A' of the single-stranded connecting bridge sequence A. The CD40 aptamer is connected to the 3' end of the a sequence through the complementary pairing of the complementary sequence A' and the single-stranded connecting bridge sequence A. Preferably, the sequence of CpG2006 is: SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thio modification in the phosphate backbone between adjacent nucleotides; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 156: GCCAACGAGTAGGCGATAGCGCGTGGC, wherein the phosphate backbone between the first 4 adjacent nucleotides at the 5' end is thiolated; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, and the phosphate backbone between the first 4 adjacent nucleotides at the 5' end is thiolated; Preferably, the transition sequence is TTTTT; iv) CCPD3-variant 8, a sequence is: SEQ ID NO: 18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC; b sequence is: SEQ ID NO: 19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG; c sequence is: SEQ ID NO:31: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGC; The CpG2006 is connected to the 5' end of the a sequence through a transition sequence, the CD40 aptamer is connected to the 5' end of the b sequence through the transition sequence, and the PD-L1 aptamer is connected to the 5' end of the c sequence through the transition sequence. Preferably, the sequence of CpG2006 is: SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thio modification in the phosphate backbone between adjacent nucleotides; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 156: GCCAACGAGTAGGCGATAGCGCGTGGC, the ribose of the first 4 nucleotides at the 5' end is modified with 2'-O-MOE, and the base of the nucleotide corresponding to Cm is modified with 5-methyl; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, the ribose of the first 4 nucleotides at the 5' end is modified with 2'-O-MOE, and the base of the nucleotide corresponding to Cm is modified with 5-methyl; Preferably, the transition sequence is TTTTT; v) CCPD3-Variant 9, a sequence is: SEQ ID NO: 18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC; b sequence is: SEQ ID NO: 19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG; c sequence is: SEQ ID NO:31: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGC; The CpG2006 is connected to the 5' end of the a sequence through a transition sequence, the CD40 aptamer is connected to the 5' end of the b sequence through the transition sequence, and the PD-L1 aptamer is connected to the 5' end of the c sequence through the transition sequence. Preferably, the sequence of CpG2006 is: SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thio modification in the phosphate backbone between adjacent nucleotides; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the ribose of the first five nucleotides at the 5' end is modified with 2'-O-MOE, and the bases of the nucleotides corresponding to the three Cms are modified with 5-methyl; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, the ribose of the first 5 nucleotides at the 5' end is modified with 2'-O-MOE, and the base of the nucleotide corresponding to 1 Cm is modified with 5-methyl; Preferably, the transition sequence is TTTTT; v) CCPD3-Variant 10, a sequence is: SEQ ID NO: 18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC; b sequence is: SEQ ID NO: 19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG; c sequence is: SEQ ID NO:31: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGC; The CpG2006 is connected to the 5' end of the a sequence through a transition sequence, the CD40 aptamer is connected to the 5' end of the b sequence through the transition sequence, and the PD-L1 aptamer is connected to the 5' end of the c sequence through the transition sequence. Preferably, the sequence of CpG2006 is: SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thio modification in the phosphate backbone between adjacent nucleotides; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the ribose of the first five nucleotides at the 5' end is modified with 2'-O-MOE, and the bases of the nucleotides corresponding to the three Cms are modified with 5-methyl; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 249: CTACGAGACGAACTTATGCGTAATAATGACTGTCGTAG, the ribose of the first 5 nucleotides at the 5' end is modified with 2'-O-MOE, and the base of the nucleotide corresponding to 1 Cm is modified with 5-methyl; Preferably, the transition sequence is TTTTT; vii) CCPD3-Variant 11, a sequence is: SEQ ID NO: 18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC; b sequence is: SEQ ID NO: 19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG; The c sequence is: SEQ ID NO: 299: CGCGGCTCGCGGCTCGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the underlined portion is a connecting bridge sequence; CpG2006 is connected to the 5' end of the a sequence through a transition sequence, the CD40 aptamer is connected to the 5' end of the b sequence through a transition sequence, the PD-L1 aptamer is connected to the 3' end of the complementary sequence of the connecting bridge sequence SEQ ID NO:14: AGCCGCGAGCCGCG, and is connected to the 5' end of the c sequence through the complementary sequence of the connecting bridge sequence and the complementary pairing of the connecting bridge sequence. Preferably, the sequence of CpG2006 is: SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thio modification in the phosphate backbone between adjacent nucleotides; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, with 2'-O-MOE modification on the ribose of the first 5 nucleotides at the 5' end; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, and there is a 2'-O-MOE modification on the ribose of the first 1-5 nucleotides at the 3' end; Preferably, the transition sequence is TTTTT. viii) CCPD3-Variant 12, a sequence is: SEQ ID NO: 18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC; b sequence is: SEQ ID NO: 19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG; The c sequence is: SEQ ID NO: 299: CGCGGCTCGCGGCTCGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the underlined portion is a connecting bridge sequence; CpG2006 is connected to the 5' end of the a sequence through a transition sequence, the CD40 aptamer is connected to the 5' end of the b sequence through a transition sequence, the PD-L1 aptamer is connected to the 3' end of the complementary sequence of the connecting bridge sequence SEQ ID NO:14: AGCCGCGAGCCGCG through a transition sequence, and is connected to the 5' end of the c sequence through a complementary sequence of the connecting bridge sequence and a complementary pairing with the connecting bridge sequence. Preferably, the sequence of CpG2006 is: SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thio modification in the phosphate backbone between adjacent nucleotides; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, with 2'-O-MOE modification on the ribose of the first 5 nucleotides at the 5' end; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 249: CTACGAGACGAACTTATGCGTAATAATGACTGTCGTAG, with 2'-O-MOE modification on the ribose of the first 1-5 nucleotides at the 3' end; Preferably, the transition sequence is TTTTT; Drug 12): CD16a aptamer-CTLA4 aptamer-CpG2006-DNA vector, wherein, The DNA vector is selected from the group 4) of the nucleic acid vectors described in claim 4, the CD16a aptamer is connected to the 5' end of the a sequence through the transition sequence, the CTLA-4 aptamer is connected to the 5' end of the b sequence through the transition sequence; the CpG2006 is connected to the 5' end of the c sequence through the transition sequence, wherein, In the DNA vector, the phosphate backbone between the 3' end of the a sequence, the 3' end of the b sequence and the first two nucleotides of the 3' end of the c sequence is thiolated; Preferably, the sequence of the CD16a aptamer is: SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated; Preferably, the sequence of the CTLA-4 aptamer is: SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU, the phosphate backbone between the first two nucleotides at the 5' end is thio-modified, C and U are 2'-F modified, and A and G are 2'-OME modified; Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the transition sequence is TTTTT; Drug 13): 2*CpG2006-CD40 aptamer-PD-L1 aptamer-C12 aptamer-DNA vector, wherein, The DNA vector is selected from the 5th group of the nucleic acid vector described in claim 4, the two CpG2006 are connected to the 5' end of the a sequence and the c sequence respectively through a transition sequence, and the CD40 aptamer is located at the 5' end of the b sequence, wherein, In the DNA vector, the phosphate backbone between the 3' end of the a sequence, the 3' end of the b sequence and the first two nucleotides of the 3' end of the c sequence is thiolated; The PD-L1 aptamer is sequentially connected to the transition sequence and the complementary sequence B' of the single-stranded bridge sequence B, the single-stranded bridge sequence B is located at the 3' end of the b sequence, and the PD-L1 aptamer is connected to the 3' end of the b sequence through the complementary pairing of the complementary sequence B' and the single-stranded bridge sequence B. The C12 aptamer is sequentially connected to the transition sequence and the complementary sequence C' of the single-stranded bridge sequence C, the single-stranded bridge sequence C is located at the 3' end of the c sequence, and the C12 aptamer is connected to the 3' end of the c sequence through the complementary pairing of the complementary sequence C' and the single-stranded bridge sequence C; Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the transition sequence is TTTTT; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the phosphate backbone between the first three adjacent nucleotides at the 5' end is thiolated; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, the phosphate backbone between the first three adjacent nucleotides at the 5' end is thiolated; Preferably, the sequence of the C12 aptamer is: SEQ ID NO: 164: GTGGATTGTTGTGTTCTGTTGGTTTTTGTGTTGTC, the phosphate backbone between the first three adjacent nucleotides at the 5' end is thiolated; Preferably, the single-stranded connecting bridge sequence B is: SEQ ID NO: 7: TGTAGCACGGTGGC, and the complementary sequence B' is SEQ ID NO: 8: GCCACCGTGCTACA; Preferably, the single-stranded connecting bridge sequence C is: SEQ ID NO: 11: TGCTGCTGCTGCTG, and the complementary sequence C' is SEQ ID NO: 12: CAGCAGCAGCAGCA; Drug 14): CpG2006-C12 aptamer-CD47 siRNA-PD-L1 aptamer-PD-L1 siRNA-DNA vector, wherein, The DNA vector is selected from the group 6) of the nucleic acid vectors described in claim 4, wherein the CpG2006 is connected to the 5' end of the a sequence through a transition sequence, the C12 aptamer is connected to the antisense strand of the CD47 siRNA through a transition sequence, the sense strand of the CD47 siRNA is located at the 5' end of the b sequence, the antisense strand of the CD47 siRNA is complementary to the sense strand of the CD47 siRNA, and the C12 aptamer and the CD47 siRNA are connected to the 5' end of the b sequence, the sense strand of the PD-L1 siRNA is connected to the 5' end of the c sequence, and the PD-L1 aptamer and the antisense strand of the PD-L1 siRNA are connected through the transition sequence, wherein, In the DNA vector, the phosphate backbone between the 3' end of the a sequence, the 3' end of the b sequence and the first 3 nucleotides of the 3' end of the c sequence is thiolated; Preferably, the sequence of the C12 aptamer is: SEQ ID NO: 164: GTGGATTGTTGTGTTCTGTTGGTTTTTGTGTTGTC, the phosphate backbone between the first three adjacent nucleotides at the 5' end is thiolated; Preferably, the antisense strand of the CD47 siRNA is: SEQ ID NO:79: AUAUCUCUGGGUAAUCACCUU, the sense strand is: SEQ ID NO:78: GGUGAUUACCCAGAGAUAUUU, the phosphate backbone between the first 3 adjacent nucleotides at the 5' end of the antisense strand of the CD47 siRNA is thiolated, the phosphate backbone between the first 3 adjacent nucleotides at the 5' end of the sense strand of the CD47 siRNA is thiolated, and the phosphate backbone between the first 3 adjacent nucleotides at the 3' end is thiolated; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 239: GCCCCAGTTATGCTTTCCCCCTCTGTCTCTTTG, the phosphate backbone between the first three adjacent nucleotides at the 5' end is thiolated; Preferably, the sense strand of the PD-L1 siRNA is: SEQ ID NO:94: CCAGCACACUGAGAAUCAAUU, and the antisense strand is: SEQ ID NO:95: UUGAUUCUCAGUGUGCUGGUU, the phosphate backbone between the first 3 adjacent nucleotides at the 5' end of the sense strand of the PD-L1 siRNA is thiolated, and the phosphate backbone between the first 3 adjacent nucleotides at the 3' end of the sense strand of the PD-L1 siRNA is thiolated; the phosphate backbone between the first 3 adjacent nucleotides at the 5' end of the antisense strand of the PD-L1 siRNA is thiolated; Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the transition sequence is TTTTT; Drug 15): 2*CpG2006-CD40 aptamer-CD16a aptamer-DNA vector, wherein, The DNA vector is selected from the group 7) of the nucleic acid vectors described in claim 4, wherein the two CpG2006 are connected to the 5' end of the a sequence and the c sequence respectively through the transition sequence, the CD40 aptamer is connected to the 5' end of the b sequence through the transition sequence, and the CD16a aptamer is connected to the 3' end of the b sequence through the transition sequence, wherein: There is a thiolation modification on the phosphate backbone between the first two nucleotides at the 3' end of the a sequence and the c sequence of the DNA vector; Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the transition sequence is TTTTT; Preferably, the sequence of the CD16a aptamer is: SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the phosphate backbone between the first two nucleotides at the 3' end is thiolated; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the phosphate backbone between the last two nucleotides at the 5' end is thiolated; Drug 16): 2*CpG2006-CD40 aptamer-CD16a aptamer-FAP aptamer-DNA vector, wherein, The DNA vector is selected from the group 8) of the nucleic acid vectors described in claim 4, wherein the two CpG2006s are connected to the 5' ends of the a sequence and the c sequence respectively through the transition sequence, the CD40 aptamer is connected to the 5' end of the b sequence through the transition sequence, the CD16a aptamer is connected to the 3' end of the b sequence through the transition sequence, and the FAP aptamer is connected to the 3' end of the c sequence through the transition sequence, wherein: The phosphate backbone between the first two nucleotides at the 3' end of the a sequence of the DNA vector is thiolated; Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the transition sequence is TTTTT; Preferably, the sequence of the CD16a aptamer is: SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the phosphate backbone between the first two nucleotides at the 3' end is thiolated; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the phosphate backbone between the last two nucleotides at the 5' end is thiolated; Preferably, the sequence of the FAP aptamer is: SEQ ID NO: 188: CCGCTCGAGCTAGTCTGACAAAGAGAAACAC, the phosphate backbone between the last two nucleotides at the 3' end is thiolated; Drug 17): 2*CpG2006-VEGF aptamer-CD40 aptamer-PD-L1 aptamer-CD16a aptamer-DNA vector, wherein, The DNA vector is selected from the group 6) of the nucleic acid vectors described in claim 4, wherein the two CpG2006s are connected to the 5' ends of the a sequence and the c sequence respectively through the transition sequence, the CD40 aptamer is connected to the 5' end of the b sequence through the transition sequence, the PD-L1 aptamer is connected to the 3' end of the b sequence through the transition sequence, the CD16a aptamer is connected to the 3' end of the c sequence through the transition sequence, and the VEGF aptamer is connected to the 3' end of the a sequence through the transition sequence. Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the VEGF aptamer: SEQ ID NO: 279: GGTGGGGGTGGACGGGCCGGGTAGA, the phosphate backbone between the last two nucleotides at the 3' end is thiolated; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the phosphate backbone between the first two nucleotides at the 5' end is thiolated; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, and the phosphate backbone between the last 2 nucleotides at the 3' end is thiolated; Preferably, the sequence of the CD16a aptamer is: SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, and the phosphate backbone between the last two nucleotides at the 3' end is thiolated; Drug 18): 2*AmiR21-TTA1 aptamer-DNA vector, wherein the DNA vector is the group 13) in the nucleic acid vector of claim 4, 2 AmiR21s are directly connected to the 5' end of the a sequence and the c sequence respectively, and the TTA1 aptamer is connected to the 5' end of the b sequence via a transition sequence, Preferably, the transition sequence is TTTTT; Preferably, the sequence of AmiR21 is GATAAGCT, and each nucleotide has a locked nucleic acid modification; Preferably, the sequence of the TTA1 aptamer is: SEQ ID NO: 266: CTGCACTTGGCTTGGATTTCAGAAGGGAGACCC; Drug 19): 2*AmiR-21-3*biotin-DNA vector, wherein, The DNA vector is the 13th group of the nucleic acid vector according to claim 4, wherein two AmiR21s are directly connected to the 5' ends of the a sequence and the c sequence, respectively, and three biotins are connected to the 5' end and the 3' end of the b sequence and the 3' end of the c sequence, respectively. Preferably, the sequence of AmiR-21 is GATAAGCT, wherein each nucleotide is modified with a locked nucleic acid; Drug 20): 2*AmiR-21-4*biotin-DNA vector, wherein, The DNA vector is the 13th group of the nucleic acid vector according to claim 4, wherein two AmiR21s are directly connected to the 5' ends of the a sequence and the c sequence, respectively, and four biotins are connected to the 3' end of the a sequence, the 5' end and the 3' end of the b sequence, and the 3' end of the c sequence, respectively. Preferably, the sequence of AmiR-21 is GATAAGCT, wherein each nucleotide is modified with a locked nucleic acid; Drug 21): 2*AmiR-21-AS1411 aptamer-DNA vector, wherein, The DNA vector is the 13th group of the nucleic acid vector according to claim 4, wherein two AmiR21s are directly connected to the 5' ends of the a sequence and the c sequence, respectively, and the AS1411 adapter is connected to the 5' end of the b sequence via a transition sequence. Preferably, the transition sequence is TTTTT; Preferably, the sequence of AmiR-21 is GATAAGCT, wherein each nucleotide is modified with a locked nucleic acid; Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG; Drug 22): 2*AmiR-21-AS1411 aptamer-DNA vector, wherein, The DNA vector is the group 23) of the nucleic acid vector according to claim 4, wherein two AmiR-21s are directly connected to the 5' end of the a sequence and the c sequence respectively, and the AS1411 adapter is connected to the 5' end of the b sequence via a transition sequence. Preferably, the transition sequence is TTTTT; Preferably, the sequence of AmiR-21 is GATAAGCT, wherein positions 1 and 3-5 have 2'-OME modifications, and positions 2 and 6-8 have 2'-F modifications; Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG; Drug 23): 2*AmiR-21-AS1411 aptamer-biotin-DNA vector, wherein, The DNA vector is the 13th group of the nucleic acid vector according to claim 4, wherein the two AmiR-21s are directly connected to the a sequence and The 5' end of the c sequence, the AS1411 aptamer is connected to the 5' end of the b sequence through a transition sequence, and the biotin is connected to the 3' end of the c sequence; Preferably, the transition sequence is TTTTT; Preferably, the sequence of AmiR-21 is GATAAGCT, wherein each nucleotide is modified with a locked nucleic acid; Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG; Drug 24): 2*AmiR-21-CD40 aptamer-DNA vector, wherein, The DNA vector is the 13th group of the nucleic acid vector according to claim 4, wherein two AmiR-21s are directly connected to the 5' end of the a sequence and the c sequence, respectively, and the CD40 aptamer is connected to the 5' end of the b sequence via a transition sequence; Preferably, the transition sequence is TTTTT; Preferably, the sequence of AmiR-21 is GATAAGCT, wherein each nucleotide is modified with a locked nucleic acid; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG; Drug 25): 2*AmiR-21-MUC1 aptamer-3*biotin-DNA vector, wherein, The DNA vector is the 13th group of the nucleic acid vector according to claim 4, wherein two AmiR21s are directly connected to the 5' end of the a sequence and the c sequence, respectively, and the MUC1 adapter is connected to the 5' end of the b sequence via a transition sequence; Preferably, the transition sequence is TTTTT; Preferably, the sequence of AmiR-21 is GATAAGCT, wherein each nucleotide is modified with a locked nucleic acid; Preferably, the sequence of the MUC1 aptamer is: SEQ ID NO: 208: GCAGTTGATCCTTTGGATACCCTGG; Drug 26): AmiR-21-AS1411 aptamer-A15 aptamer-2*biotin-DNA vector, wherein, The DNA vector is the 13th group of the nucleic acid vector according to claim 4, wherein the AmiR21 is directly connected to the 5' end of the a sequence, the AS1411 aptamer and the A15 aptamer are respectively connected to the 5' end of the b sequence and the 5' end of the c sequence through transition sequences, and the two biotins are respectively connected to the 3' end of the b sequence and the 3' end of the c sequence; Preferably, the transition sequence is TTTTT; Preferably, the sequence of AmiR-21 is GATAAGCT, wherein each nucleotide is modified with a locked nucleic acid; Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG; Preferably, the sequence of the A15 aptamer is: SEQ ID NO: 129: CCCTCCTACATAGGG; Drug 27): 2*mannose-2*AmiR-21-DNA vector, wherein, The DNA vector is the 13th group of the nucleic acid vector according to claim 4, wherein the two mannoses are respectively connected to the 5' end and the 3' end of the b sequence, and the two AmiR-21s are directly connected to the 5' end of the a sequence and the c sequence respectively; Preferably, the sequence of AmiR-21 is GATAAGCT, wherein each nucleotide is modified with a locked nucleic acid; Drug 28): 2*mannose-A15 aptamer-2*AmiR-21-DNA vector, wherein, The DNA vector is the 13th group of the nucleic acid vector according to claim 4, the A15 aptamer is connected to the 5' end of the b sequence through a transition sequence, the two mannoses are respectively connected to the 5' end of the A15 aptamer and the 3' end of the b sequence, and the two AmiR-21s are directly connected to the 5' end of the a sequence and the c sequence respectively; Preferably, the sequence of AmiR-21 is GATAAGCT, wherein each nucleotide is modified with a locked nucleic acid; Preferably, the sequence of the A15 aptamer is: SEQ ID NO: 129: CCCTCCTACATAGGG; Drug 29): 2* mannose-survivin siRNA-DNA vector, wherein, The DNA vector is the 13th group of the nucleic acid vector according to claim 4, wherein the two mannoses are respectively connected to the 5' end and the 3' end of the b sequence, the sense strand of the survivin siRNA is connected to the 3' end of the c sequence, and the antisense strand of the survivin siRNA is connected to the 3' end of the c strand by complementary pairing with the sense strand of the survivin siRNA; Preferably, the positive strand of the survivin siRNA is: SEQ ID NO: 104: UGCAGGUUCCUUAUCUGUCATT, The antisense strand of the survivin siRNA is: SEQ ID NO: 105: UGACAGAUAAGGAACCUGCTT, and the 3' end TT of the sense strand and the antisense strand of the survivin siRNA are both modified with dTdT; Drug 30): 2* mannose-A15 aptamer-survivin siRNA-DNA vector, wherein, The DNA vector is the group 22) of the nucleic acid vector according to claim 4, the A15 aptamer is connected to the 5' end of the b sequence through the transition sequence TTTTT, the two mannoses are respectively connected to the 5' end of the A15 aptamer and the 3' end of the b sequence, the sense strand of the survivin siRNA is connected to the 3' end of the c strand, and the antisense strand of the survivin siRNA is connected to the 3' end of the c strand by complementary pairing with the sense strand of the survivin siRNA; Preferably, the sense strand of the survivin siRNA is: SEQ ID NO: 104: UGCAGGUUCCUUAUCUGUCATT; The antisense strand of the survivin siRNA is: SEQ ID NO: 105: UGACAGAUAAGGAACCUGCTT; the TT at the 3' end of the antisense strand and the sense strand of the survivin siRNA are both modified with dTdT; Preferably, the sequence of the A15 aptamer is: SEQ ID NO: 129: CCCTCCTACATAGGG; Drug 31): AS1411 aptamer-survivin siRNA-PSMA aptamer-3*AmiR-21-RNA vector, wherein, The DNA vector is the nucleic acid vector of claim 4, wherein the PSMA aptamer is connected to the 3' end of the a sequence via the transition sequence AA, the three AmiR-21s are connected in series to the 3' end of the b sequence via the transition sequence AA, the positive strand of the survivin siRNA is connected to the 3' end of the c sequence via the transition sequence AAA. The AS1411 aptamer is connected to the 3' end of the c sequence through the transition sequence TT, and is connected to the 3' end of the c sequence through the complementary pairing of the antisense strand of the survivin siRNA and the sense strand of the survivin siRNA, wherein, The first two nucleotides at the 5' end of the a sequence, the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG; Preferably, the sense strand of the survivin siRNA is: SEQ ID NO: 100: GCAGGUUCCUUAUCUGUCACAUU, the antisense strand of the survivin siRNA is: SEQ ID NO: 300: UGUGACAGAUAAGGAACCUGCAG, and both the sense strand and the antisense strand of the survivin siRNA have thiolation modifications between the first 3 positions of the 5' end and the last 3 positions of the 3' end; Preferably, the sequence of the PSMA aptamer is: SEQ ID NO: 234: GGGACCGAAAAAGACCUGACUUCUAUACUAAGUCUACGUUCCC, and there is a thiolation modification on the phosphate backbone between the last two nucleotides at the 3' end; Preferably, the sequence of AmiR-21 is: GAUAAGCU, and there is a thio modification in the phosphate backbone between adjacent nucleotides; Drug 32): 3*AmiR-21-ATP aptamer-FGF2 aptamer-DNA vector, wherein, The DNA vector is the 15th group of the nucleic acid vector according to claim 4, wherein the three AmiR-21s are directly connected in series to the 5' end of the a sequence, the ATP aptamer is connected to the 5' end of the b sequence via the transition sequence TTTTT, and the FGF2 aptamer is connected to the 5' end of the c sequence via U, wherein: The first two nucleotides at the 3' end of the a sequence, the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the ATP aptamer is: SEQ ID NO: 135: ACCTGGGGAGTATTGGGGAGGAAGG, and the phosphate backbone between the first two nucleotides at the 5' end is thiolated; Preferably, the sequence of the FGF2 aptamer is: SEQ ID NO: 183: GGGAUACUAGGGCAUUAAUGUUACCAGUGUAGUCCC, and the phosphate backbone between the first two nucleotides at the 5' end is thiolated; Preferably, the sequence of AmiR-21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides; Drug 33): AS1411 aptamer-Survivin siRNA-PSMA aptamer-3*AmiR-21-DNA-RNA mixed vector, wherein, The DNA-RNA hybrid vector is the 18th group of the nucleic acid vector according to claim 4, wherein the PSMA aptamer is connected to the 3' end of the a sequence through the transition sequence AA, the three AmiR-21s are connected in series to the 3' end of the b sequence through the transition sequence AA, the positive strand of the Survivin siRNA is connected to the 3' end of the c sequence through the transition sequence AAAA, the AS1411 aptamer is connected to the 5' end of the antisense strand of the Survivin siRNA through the transition sequence AA, and the antisense strand of the Survivin siRNA is connected to the Survivin siRNA. The positive strands are complementary and paired, where The first two nucleotides at the 5' end of the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Preferably, the antisense strand of the Survivin siRNA is: SEQ ID NO: 300: UGUGACAGAUAAGGAACCUGCAG; the sense strand is: SEQ ID NO: 100: GCAGGUUCCUUAUCUGUCACAUU; both the sense strand and the antisense strand of the Survivin siRNA have thiolation modifications in the phosphate backbone between the first 3 adjacent nucleotides at the 5' end and between the last 3 adjacent nucleotides at the 3' end; Preferably, the sequence of the PSMA aptamer is: SEQ ID NO: 234: GGGACCGAAAAAGACCUGACUUCUAUACUAAGUCUACGUUCCC, C and U have 2'-F, A and G have 2'-OME modification, and there is a thio modification on the phosphate backbone between the first 2 nucleotides at the 3' end; Preferably, the sequence of AmiR-21 is: GAUAAGCU, and there is a thio modification in the phosphate backbone between adjacent nucleotides; Drug 34): 3*AmiR-21-AS1411 aptamer-FAP aptamer-DNA vector, wherein, The RNA vector is the 15th) group of the nucleic acid vector according to claim 4, wherein the three AmiR-21s are connected in series to the 5' end of the a sequence through the transition sequence TTTTTT, the AS1411 aptamer is connected to the 5' end of the b sequence through the transition sequence TTTTT, and the FAP aptamer is connected to the 5' end of the c sequence through the transition sequence TTTTT; Preferably, the sequence of AmiR-21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides; Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Preferably, the sequence of the FAP aptamer is: SEQ ID NO: 188: CCGCTCGAGCTAGTCTGACAAAGAGAAACAC, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Drug 35): AS1411 aptamer-Survivin siRNA-EpCAM aptamer-3*AmiR-21-DNA vector, wherein, The DNA vector is the 14th group of the nucleic acid vector according to claim 4, wherein the AS1411 aptamer is connected to the 5' end of the antisense strand of the Survivin siRNA via a transition sequence AA, the positive strand of the Survivin siRNA is connected to the 3' end of the c sequence via a transition sequence AAAA, and the antisense strand of the Survivin siRNA is connected to the 5' end of the Survivin siRNA. The siRNA positive strands are complementary and paired; the three AmiR-21s are connected in series to the 3' end of the b sequence through the transition sequence AA, and the EpCAM aptamer is connected to the 3' end of the a sequence through the transition sequence AA, wherein, The first two nucleotides at the 5' end of the b sequence of the DNA vector are independently thiolated; Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Preferably, the Survivin siRNA antisense strand is: SEQ ID NO: 300: UGUGACAGAUAAGGAACCUGCAG, the Survivin siRNA sense strand is: SEQ ID NO: 100: GCAGGUUCCUUAUCUGUCACAUU, the sense strand and antisense strand of the Survivin siRNA are both thiolated between the first 3 adjacent positions at the 5' end and between the last 3 adjacent positions at the 3' end, the 5' end of the Survivin siRNA antisense strand has 2'-F modification at the 2nd, 6th, 8th, 9th, 12th, 14th, and 16th positions, and the rest are 2'-OMe modified, the 7th, 9th, 10th, and 11th positions of the Survivin siRNA sense strand are 2'-F modification, and the rest are 2'-OMe modified; Preferably, the sequence of AmiR-21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides; Preferably, the sequence of the EpCAM aptamer is: SEQ ID NO: 179: GCGACUGGUUACCCGGUCG, C and U have 2'-F modification, A and G have 2'-OME modification; There is thiolation modification in the phosphate backbone between the first 3 positions of the 5' end and the last 3 positions of the 3' end; Drug 36): IL-4RA aptamer-TGF-β aptamer-PD-L1 aptamer-2*AmiR-21-DNA vector, wherein, The DNA vector is group 15) of the nucleic acid vector according to claim 4, wherein the IL-4RA aptamer is connected to the 5' end of the a sequence via one of the AmiR-21s, the TGF-β aptamer is connected to the 5' end of the b sequence via the transition sequence TTTTT, and the PD-L1 aptamer is connected to the 5' end of the c sequence via one of the AmiR-21s, wherein: The first two nucleotides at the 3' end of the a sequence, the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the IL-4RA aptamer is: SEQ ID NO: 203: AAAAAGCAACAGGGUGCUCCAUGCGCAUGGAACCUGCGCG, wherein the phosphate backbone between the first 4 adjacent nucleotides at the 5' end is thiolated; Preferably, the sequence of the TGF-β aptamer is: SEQ ID NO: 269: ACATTGCTGCGTGATCGCCTCACATGGGTTTGTCTGGTCGATTTGGAGGTGGTGGGTGGC, and the phosphate backbone between the first 4 adjacent nucleotides at the 5' end is thiolated; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, and the phosphate backbone between the first 4 adjacent nucleotides at the 5' end is thiolated; Preferably, the sequence of AmiR-21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides; Drug 37): AS1411 aptamer-ATAD2 siRNA-GPC3 aptamer-5*AimR-21-DNA vector, wherein, The DNA vector is the 19th group of the nucleic acid vector described in claim 4, wherein the AS1411 aptamer is connected to the 5' end of the antisense strand of the ATAD2 siRNA via one AimR-21, the sense strand of the ATAD2 siRNA is connected to the 3' end of the c sequence via one AimR-21, the antisense strand of the ATAD2 siRNA is complementary to the sense strand of the ATAD2 siRNA, one AimR-21 is connected to the 3' end of the a sequence, the GPC3 aptamer is connected to the 5' end of the b sequence via one AimR-21, and one AimR-21 is connected to the 5' end of the c sequence, wherein: The first two nucleotides at the 5' end of the b sequence of the DNA vector are independently thiolated; Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Preferably, the antisense strand of the ATAD2 siRNA is: SEQ ID NO:68: GCGUCGAAGUUGUAGGAUUUU, and the sense strand is: SEQ ID NO:69: AAUCCUACAACUUCGACGCUU, and the sense strand and antisense strand of the ATAD2 siRNA are both thiolated between the first 3 adjacent positions at the 5' end and the last 3 adjacent positions at the 3' end, and the 2nd, 6th, 8th, 9th, 12th, 14th, and 16th positions from the 5' end are 2'-F modified, and the rest are 2'-OME modified; The sequence of the GPC3 aptamer is: SEQ ID NO: 190: TAACGCTGACCTTAGCTGCATGGCTTTACATGTTCCA, with a thiolation modification of the phosphate backbone between the first three adjacent nucleotides at the 5' end; Preferably, the sequence of AmiR-21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides; Drug 38): Vap7 aptamer-TGF-β aptamer-Act-12c aptamer-3*AmiR-21-DNA vector, wherein, The DNA vector is group 15) of the nucleic acid vector according to claim 4, wherein the Vap7 aptamer is connected to the 5' end of the a sequence via two tandem AmiR-21s, the TGF-β aptamer is connected to the 5' end of the b sequence via a transition sequence TTTTT, and the Act-12c aptamer is connected to the 5' end of the c sequence via one AmiR-21, wherein: The first two nucleotides at the 3' end of the a sequence, the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the Vap7 aptamer is: SEQ ID NO: 277: TGGTGGGGGTGGACGGGCCGGGTAGA, wherein there is a thiolation modification in the phosphate backbone between the first 4 adjacent nucleotides at the 5' end; Preferably, the sequence of AmiR-21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides; Preferably, the sequence of the TGF-β aptamer is: SEQ ID NO: 269: ACATTGCTGCGTGATCGCCTCACATGGGTTTGTCTGGTCGATTTGGAGGTGGTGGGTGGC, wherein there is a thiolation modification in the phosphate backbone between the first 4 adjacent nucleotides at the 5' end; Preferably, the sequence of the Act-12c aptamer is: SEQ ID NO: 137: CGGGGAAAGTCACGGGGGGTTTCAGATGTTCTGATCGGTGTGGAG, wherein there is a thiolation modification in the phosphate backbone between the first 4 adjacent nucleotides at the 5' end; Drug 39): AS1411 aptamer-3*AmiR-21-IL-4RA aptamer-VCAM-1 aptamer-DNA vector, wherein, The DNA vector is the 15th group of the nucleic acid vector according to claim 4, wherein the AS1411 aptamer is sequentially connected to the 5' end of the a sequence through the transition sequence TTTTT and three tandem AmiRs, and the IL-4RA aptamer and the VCAM-1 aptamer are respectively connected to the 5' end of the b sequence and the 5' end of the c sequence through the transition sequence TTTTT, wherein: The first two nucleotides at the 3' end of the a sequence, the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: G*GTGGTGGTGGTTGTGGTGGTGGTGG, wherein there is a thiolation modification in the phosphate backbone between the first 2 nucleotides at the 5' end; Preferably, the sequence of AmiR-21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides; Preferably, the sequence of the IL-4RA aptamer is: SEQ ID NO: 203: AAAAAGCAACAGGGUGCUCCAUGCGCAUGGAACCUGCGCG, wherein the phosphate backbone between the first two nucleotides at the 5' end has a thio modification, and C or U has a 2'-F modification, and A or G has a 2'-OME modification; Preferably, the sequence of the VCAM-1 aptamer is: SEQ ID NO: 284: GGACACGGCAAAGGGGTATAGCCTACCGGACCGTGAACATGGAATGGTGTGCTGCGTGG, wherein there is a thiolation modification in the phosphate backbone between the first two nucleotides at the 5' end; Drug 40): GPC1 aptamer-AS1411 aptamer-EpCAM aptamer-2*AmiR-21-DNA vector, wherein, The DNA vector is the 14th group of the nucleic acid vector according to claim 4, wherein the GPC1 aptamer is connected to the 5' end of the a sequence via one of the AmiR-21s, the AS1411 aptamer is connected to the 5' end of the b sequence via the transition sequence TTTTT, and the EpCAM aptamer is connected to the 5' end of the c sequence via one of the AmiR-21s, wherein: The first three nucleotides at the 3' end of the a sequence, the b sequence and the c sequence of the DNA vector are independently thiolated, and the first two nucleotides at the 3' end are independently 2'-O-MOE modified; Preferably, the sequence of the GPC1 aptamer is: SEQ ID NO: 189: AACGGAGTGTGGCTAACTCGA, wherein there is a thiolation modification in the phosphate backbone between the first 4 adjacent nucleotides at the 5' end; Preferably, the sequence of AmiR-21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides; Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, with thiolation modification present in the phosphate backbone between nucleotides 1-2, 3-4, 13-14, 16-17 and 24-25 from the 5' end; Preferably, the sequence of the EpCAM aptamer is: SEQ ID NO: 179: GCGACUGGUUACCCGGUCG, wherein the phosphate backbone between the first 4 adjacent nucleotides at the 5' end has a thio modification, and C or U has a 2'-F modification, and A or G has a 2'-OME modification; Drug 41): 3*AmiR-21-AS1411 aptamer-CD40 aptamer-2*biotin-DNA vector, wherein, The DNA vector is selected from the first group of nucleic acid vectors described in claim 4, the three AmiR-21s are respectively connected to the 5' end, the 3' end and the 3' end of the a sequence, the AS1411 aptamer is connected to the 5' end of the b sequence via the transition sequence TTTTT, the CD40 aptamer is connected to the 5' end of the c sequence via the transition sequence TTTTT, one of the biotins is modified at the 3' end of the AmiR-21 located at the 3' end of the a sequence, and another one of the biotins is modified at the 3' end of the c sequence; Preferably, the sequence of AmiR-21 is: GATAAGCT, each nucleotide has a locked nucleic acid modification; Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG; Drug 42): IL-4RA aptamer-VCAM-12d aptamer-PD-L1 aptamer-3*AmiR-21-DNA vector, wherein, The DNA vector is selected from the group 3) of the nucleic acid vectors described in claim 4, the IL-4RA aptamer is connected to the 5' end of the a sequence through the first AmiR21, the VCAM-1 aptamer is connected to the 5' end of the b sequence through the second AmiR21, and the PD-L1 aptamer is connected to the 5' end of the c sequence through the third AmiR21, wherein The first two nucleotides at the 3' end of the a sequence, the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the IL-4RA aptamer is: SEQ ID NO: 203: AAAAAGCAACAGGGUGCUCCAUGCGCAUGGAACCUGCGCG, with the first 4 adjacent nucleobases at the 5' end There is a thio modification on the phosphate backbone between nucleotides, and C or U has a 2'-F modification, and A or G has a 2'-OME modification; Preferably, the sequence of the VCAM-12d aptamer is: SEQ ID NO: 285: AGGGAATCTTGCCTAGGGAGGGAGTAGCGAAAGGGCTCA, a thiolation modification exists in the phosphate backbone between the first 4 adjacent nucleotides at the 5' end; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, and there is a thiolation modification in the phosphate backbone between the first 4 adjacent nucleotides at the 5' end; Preferably, the sequence of AmiR-21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides; Drug 43): TAPsiRNA-3*AmiR-21-2*AS1411 aptamer-DNA vector, wherein, The DNA vector is selected from the group 6) of the nucleic acid vectors described in claim 4, the sense strand of the TAPsiRNA is connected to the 3' end of the c sequence through a transition sequence AAAA, one of the AS1411 aptamers is connected to the antisense strand of the TAPsiRNA through a transition sequence AAAA, and the AS1411 aptamer is connected to the 3' end of the c sequence through complementary pairing of the antisense strand and the sense strand, another AS1411 aptamer is connected to the 3' end of the a sequence through a transition sequence AAAA, and three AmiR-21s are connected in series to the 3' end of the b sequence through a transition sequence AA, and the first two nucleotides at the 5' end of the a sequence, the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sense strand sequence of the TAPsiRNA is: SEQ ID NO: 301: GCUGCACACGGUUCAGAAU, and the antisense strand sequence is: SEQ ID NO: 109: AUUCUGAACCGUGUGCAGCUU, and both the sense strand and the antisense strand of the TAPsiRNA are thiolated between the first 3 bases at the 5' end and the last 3 bases at the 3' end, the 2nd, 6th, 8th, 9th, 12th, 14th, and 16th bases at the 5' end of the antisense strand of the TAPsiRNA are 2'-F modified, and the rest are 2'-OME modified, and the 7th, 9th, 10th, and 11th bases at the 5' end of the sense strand of the TAPsiRNA are 2'-F modified, and the rest are 2'-OME modified; Preferably, the sequence of AmiR-21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides; Preferably, the sequence of AS1411-1 is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Drug 44): PD-1 aptamer-AS1411 aptamer-PD-L1 aptamer-3*AmiR-21-DNA vector, wherein, The DNA vector is selected from the group 3) of the nucleic acid vectors described in claim 4, and the PD-1 aptamer is expressed by 1 AmiR-21 is connected to the 5' end of the a sequence, the AS1411 aptamer is connected to the 5' end of the b sequence through one AmiR-21, the PD-L1 aptamer is connected to the 5' end of the c sequence through one AmiR-21, and the first two nucleotides at the 3' end of the a sequence, the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the PD-1 aptamer is: SEQ ID NO: 253: AGCGGTGACGGCACAGACGGTACAGTTCCCGTCCCTGCACTACACGTATGCCGCT, and there is a thiolation modification in the phosphate backbone between the first 4 adjacent nucleotides at the 5' end; Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, and the phosphate backbone between the first two adjacent nucleotides at the 5' end is thiolated; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, and the phosphate backbone between the first 4 adjacent nucleotides at the 5' end is thiolated; Preferably, the sequence of AmiR-21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides; Drug 45): CPG1826-CD40 aptamer-AmiR-21-3*biotin-DNA vector, wherein, The DNA vector is the 13th group of the nucleic acid vector according to claim 4, wherein the CpG1826 is connected to the 5' end of the a sequence through the transition sequence, the CD40 aptamer is connected to the 5' end of the b sequence through the transition sequence, the AmiR-21 is connected to the 5' end of the c sequence through the transition sequence, and the three biotins are connected to the 3' ends of the a sequence, the b sequence and the c sequence, respectively; Preferably, the sequence of CpG1826 is: SEQ ID NO: 59: TCCATGACGTTCCTGACG, and there is a thiolation modification on the phosphate backbone between two adjacent nucleotides; Preferably, the transition sequence is TTTTT; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG; Preferably, the sequence of AmiR21 is GATAAGCT, and each nucleotide has a locked nucleic acid modification; Drug 46): ATP aptamer-AmiR-21-FGF2 aptamer-AmiR-1306-DNA vector, wherein, In the DNA vector, the a sequence is: SEQ ID NO: 18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC; the b sequence is: SEQ ID NO: 19: GCTCCTCTCCCGGTTCGCCGCGAGCCGCG; the c sequence is: SEQ ID NO: 31: CGCGGCTCGCGGCCATAGCCGTGGGCGTCGC; the ATP aptamer is connected via a transition sequence TTTTT The FGF2 aptamer is connected to the 5' end of the a sequence, the FGF2 aptamer is connected to the 5' end of the b sequence through the transition sequence U, and the AmiR1306 and the AmiR-21 are connected to the 5' end of the c sequence in sequence. The sequence of the ATP aptamer is SEQ ID NO: 136: GGGAGGACGATGCGGAGGAAGGGTAGG, with a thiolation modification on the phosphate backbone between the first 4 nucleotides at the 5' end; The sequence of the FGF2 aptamer is SEQ ID NO: 183: GGGAUACUAGGGCAUUAAUGUUACCAGUGUAGUCCC, wherein C and U have 2′-F modifications; The sequence of AmiR1306 is: SEQ ID NO: 127: CATCACCACCAGAGCCAACGTC, wherein, The phosphate backbone between the first five nucleotides at the 5' end has a thiolation modification; The sequence of AmiR-21 is: GATAAGCT, each nucleotide is modified with a locked nucleic acid; Drug 47): CD16a aptamer-CTLA-4 aptamer-PD-L1 aptamer-DNA vector, wherein, The DNA vector is selected from the group 9) of the nucleic acid vectors described in claim 4, wherein the CD16a aptamer is connected to the 5' end of the a sequence via the transition sequence, the CTLA-4 aptamer is connected to the 5' end of the b sequence via the transition sequence, the PD-L1 aptamer is connected to the 5' end of the c sequence, and the first two nucleotides at the 3' end of the a sequence, the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the CD16a aptamer is: SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Preferably, the sequence of the CTLA-4 aptamer is: SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU, the phosphate backbone between the first two nucleotides at the 5' end has a thio modification, and C or U has a 2'-F modification, and A or G has a 2'-OME modification; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Drug 48): CD16a aptamer-Act-12c aptamer-PD-L1 aptamer-DNA vector, wherein, The DNA vector is selected from the group 9) of the nucleic acid vectors described in claim 4, the CD16a aptamer is connected to the 5' end of the a sequence through the transition sequence, and the Act-12c aptamer is connected to the b sequence through the transition sequence. The 5' end of the DNA vector is connected to the 5' end of the c sequence, and the first two nucleotides at the 3' end of the a sequence, the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the CD16a aptamer is: SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Preferably, the sequence of the Act-12c aptamer is: SEQ ID NO: 137: CGGGGAAAGTCACGGGGGGTTTCAGATGTTCTGATCGGTGTGGAG, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Drug 49): CTLA-4 aptamer-PD-L1 aptamer-PD1 aptamer-DNA vector, wherein, The DNA vector is selected from the group 5) of the nucleic acid vectors described in claim 4, The PD-L1 aptamer is sequentially connected to the transition sequence and the complementary sequence A' of the single-stranded bridge sequence A, the single-stranded bridge sequence A is located at the 3' end of the a sequence, and the PD-L1 aptamer is connected to the 3' end of the a sequence through the complementary pairing of the complementary sequence A' and the single-stranded bridge sequence A. The PD1 aptamer is sequentially connected to the transition sequence and the complementary sequence B' of the single-stranded bridge sequence B, the single-stranded bridge sequence B is located at the 3' end of the b sequence, and the PD-L1 aptamer is connected to the 3' end of the b sequence through the complementary pairing of the complementary sequence B' and the single-stranded bridge sequence B. The CTLA-4 aptamer is connected to the complementary sequence C' of the single-stranded bridge sequence C, the single-stranded bridge sequence C is located at the 3' end of the c sequence, and the PD-L1 aptamer is connected to the 3' end of the c sequence through the complementary pairing of the complementary sequence C' and the single-stranded bridge sequence C, Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, and the phosphate backbone between the first 3 adjacent nucleotides at the 5' end is thiolated; Preferably, the sequence of the PD1 aptamer is: SEQ ID NO: 254: ACCGACAGTGAAGGACTCAGCGAACTCTCAGACTCGGTTC, and the phosphate backbone between the first 3 adjacent nucleotides at the 5' end is thiolated; Preferably, the sequence of the CTLA-4 aptamer is: SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU, the phosphate backbone between the first three adjacent nucleotides at the 5' end is thio-modified, and the ribose of the first two nucleotides at the 5' end is 2'-O-MOE modified, and the remaining C or U is 2'-F modified; Preferably, the single-stranded connecting bridge sequence A is: SEQ ID NO: 7: TGTAGCACGGTGGC, and the complementary sequence A' is SEQ ID NO: 8: GCCACCGTGCTACA; Preferably, the single-stranded connecting bridge sequence B is: SEQ ID NO: 7: TGTAGCACGGTGGC, and the complementary sequence B' is SEQ ID NO: 8: GCCACCGTGCTACA; Preferably, the single-stranded connecting bridge sequence C is: SEQ ID NO: 11: TGCTGCTGCTGCTG, and the complementary sequence C' is SEQ ID NO: 12: CAGCAGCAGCAGCA; Drug 50): PD1 aptamer-IL-4Ra aptamer-OX40 aptamer-DNA vector, wherein, The DNA vector is selected from the group 6) of the nucleic acid vectors described in claim 4, the PD1 aptamer is connected to the 5' end of the a sequence through the transition sequence AAA, the IL-4Ra aptamer is connected to the 5' end of the b sequence through the transition sequence AAA, the OX40 aptamer is connected to the 5' end of the c sequence through the transition sequence AAA, and the first 3 nucleotides at the 3' end of the a sequence, the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the PD1 aptamer is: SEQ ID NO: 253: AGCGGTGACGGCACAGACGGTACAGTTCCCGTCCCTGCACTACACGTATGCCGCT, and there is a thiolation modification in the phosphate backbone between the first 4 adjacent nucleotides at the 5' end; Preferably, the sequence of the IL-4Ra aptamer is: SEQ ID NO: 203: AAAAAGCAACAGGGUGCUCCAUGCGCAUGGAACCUGCGCG, and the phosphate backbone between the first 4 adjacent nucleotides at the 5' end is thiolated; Preferably, the sequence of the OX40 aptamer is: SEQ ID NO: 229: CAGUCUGCAUCGUAGGAAUCGCCACCGUAUACUUUCCCAC, the phosphate backbone between the first 4 adjacent nucleotides at the 5' end is thio-modified, and the ribose of the first 3 nucleotides at the 5' end has a 2'-O-MOE modification, the remaining C or U has a 2'-F modification, and A or G has a 2'-OME modification; Drug 51): CD16a aptamer-OX40 aptamer-PD-L1 aptamer-DNA vector, wherein, The DNA vector is selected from the group 3) of the nucleic acid vectors described in claim 4, the CD16a aptamer is connected to the 5' end of the a sequence via a transition sequence, the OX40 aptamer is connected to the 5' end of the b sequence via a transition sequence, the PD-L1 aptamer is connected to the 5' end of the c sequence via a transition sequence, and the first two nucleotides at the 3' end of the a sequence, the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the CD16a aptamer is: SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Preferably, the sequence of the OX40 aptamer is: SEQ ID NO: 230: GGGAUGCGGAAAAAAGAACACUUCCGAUUAGGGCCCACCCUAACGGCCGCAGAC, C or U has a 2'-F modification, A or G has a 2'-OME modification, and the phosphate backbone between the first 2 nucleotides at the 5' end has a thio modification; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Drug 52): CD16a aptamer-VEGF165 aptamer-PD-L1 aptamer-DNA vector, wherein, The DNA vector is selected from the third group of nucleic acid vectors described in claim 4, wherein the CD16a aptamer is connected to the 5' end of the a sequence via a transition sequence, the VEGF165 aptamer is connected to the 5' end of the b sequence via a transition sequence, and the PD-L1 aptamer is connected to the 5' end of the c sequence via a transition sequence, and the first two nucleotides at the 3' end of the a sequence, the b sequence, and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the CD16a aptamer is: SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Preferably, the sequence of the VEGF165 aptamer is: SEQ ID NO: 280: CGGAAUCAGUGAAUGCUUAUACAUCCG, C or U has a 2'-F modification, A or G has a 2'-OME modification, and the phosphate backbone between the first 2 nucleotides at the 5' end has a thio modification; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Drug 53): CD16a aptamer-CTLA4 aptamer-TIM3 aptamer-DNA vector, wherein, The DNA vector is selected from the group 3) of the nucleic acid vectors described in claim 4, the CD16a aptamer is connected to the 5' end of the a sequence via a transition sequence, the CTLA4 aptamer is connected to the 5' end of the b sequence via a transition sequence, the TIM3 aptamer is connected to the 5' end of the c sequence via a transition sequence, and the first two nucleotides at the 3' end of the a sequence, the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the CD16a aptamer is: SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Preferably, the sequence of the CTLA4 aptamer is: SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU, the phosphate backbone between the first 2 nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification; Preferably, the sequence of the TIM3 aptamer is: SEQ ID NO: 270: GGGAGAGGACCAGUAGCCACUAUGGUGUUGGAGCUAGCGGCAGAGCGUCGCGGUCCCUCCC, the phosphate backbone between the first 2 nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification; Drug 54): PD-1 aptamer-CTLA-4 aptamer-LAG-3 aptamer-DNA vector, wherein, The DNA vector is selected from the group 3) of the nucleic acid vectors described in claim 4, the PD-L1 aptamer is connected to the 5' end of the a sequence via a transition sequence, the CTLA-4 aptamer is connected to the 5' end of the b sequence via a transition sequence, the LAG-3 aptamer is connected to the 5' end of the c sequence via a transition sequence, and the first two nucleotides at the 3' end of the a sequence, the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the PD-1 aptamer is: SEQ ID NO: 253: AGCGGTGACGGCACAGACGGTACAGTTCCCGTCCCTGCACTACACGTATGCCGCT, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Preferably, the sequence of the CTLA-4 aptamer is: SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU, the phosphate backbone between the first 2 nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification; Preferably, the sequence of the LAG-3 aptamer is: SEQ ID NO: 206: GGGAGAGAGAUAUAAGGGCCUCCUGAUACCCGCUGCUAUCUGGACCGAUCCCAUUACCAAAUUCUCUCCC, the phosphate backbone between the first two nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification; Drug 55): CD16a aptamer-Act-12c aptamer-MUC1 aptamer-DNA vector, wherein, The DNA vector is selected from the group 3) of the nucleic acid vectors described in claim 4, wherein the CD16a aptamer is connected to the 5' end of the a sequence via a transition sequence, the Act-12c aptamer is connected to the 5' end of the b sequence via the transition sequence, and the MUC1 aptamer is connected to the 5' end of the c sequence via the transition sequence, and the first two nucleotides at the 3' end of the a sequence, the b sequence, and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the CD16a aptamer is: SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Preferably, the sequence of the Act-12c aptamer is: SEQ ID NO: 137: CGGGGAAAGTCACGGGGGGTTTCAGATGTTCTGATCGGTGTGGAG, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Preferably, the sequence of the MUC1 aptamer is: SEQ ID NO: 209: GAAGTGAAAATGACAGAACACAACA; Drug 56): CD16a aptamer-TGF-β aptamer-PD-L1 aptamer-DNA vector, wherein, The DNA vector is selected from the third group of nucleic acid vectors described in claim 4, wherein the CD16a aptamer is connected to the 5' end of the a sequence via a transition sequence, the TGF-β aptamer is connected to the 5' end of the b sequence via the transition sequence, and the PD-L1 aptamer is connected to the 5' end of the a sequence via a transition sequence, and the first two nucleotides at the 3' end of the a sequence, the b sequence, and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the CD16a aptamer is: SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Preferably, the sequence of the TGF-β aptamer is: SEQ ID NO: 269: ACATTGCTGCGTGATCGCCTCACATGGGTTTGTCTGGTCGATTTGGAGGTGGTGGGTGGC, and the phosphate backbone between the first two nucleotides at the 5' end is thiolated; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Drug 57): CD16a aptamer-CD40 aptamer-CTLA-4 aptamer-DNA vector, wherein, The DNA vector is selected from the group 3) of the nucleic acid vectors described in claim 4, wherein the CD16a aptamer is connected to the 5' end of the a sequence via a transition sequence, the CD40 aptamer is connected to the 5' end of the b sequence via the transition sequence, and the CTLA-4 aptamer is connected to the 5' end of the c sequence via a transition sequence, and the first two nucleotides at the 3' end of the a sequence, the b sequence, and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the CD16a aptamer is: SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, wherein the phosphate backbone between the first two nucleotides at the 5' end is thiolated; Preferably, the sequence of the CTLA-4 aptamer is: SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU, the phosphate backbone between the first 2 nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification; Drug 58): HER2 aptamer-HER3 aptamer-CD40 aptamer-CD16a aptamer-DNA vector, wherein, The DNA vector is selected from the group 7) of the nucleic acid vectors described in claim 4, and the HER3 aptamer is The transition sequence AA is connected to the 5' end of the a sequence, the HER2 aptamer is connected to the 5' end of the c sequence through the transition sequence AA, the CD40 aptamer and the CD16a aptamer are connected to the 5' end and 3' end of the b sequence respectively through the transition sequence AA, and the first two nucleotides at the 3' end of the a sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the HER2 aptamer is: SEQ ID NO: 194: AGCCGCGAGGGGAGGGAUAGGGUAGGGCGCGGCU, the phosphate backbone between the first 2 nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification; Preferably, the sequence of the HER3 aptamer is: SEQ ID NO: 197: CAGCGAAAGUUGCGUAUGGGUCACAUCGCAGGCACAUGUCAUCUGGGCG, the phosphate backbone between the first 2 nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, wherein the phosphate backbone between the first two nucleotides at the 5' end is thiolated; Preferably, the sequence of the CD16a aptamer is: SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Drug 59): CD16a aptamer-Act-12c aptamer-CTLA-4 aptamer-GPC1 aptamer-DNA vector, wherein, The DNA vector is selected from the group 10) of the nucleic acid vectors described in claim 4, the CD16a aptamer is connected to the 5' end of the a sequence through the transition sequence TTTTT, the Act-12c aptamer is connected to the 5' end of the b sequence through the transition sequence TTTTT, the CTLA-4 aptamer and the GPC1 aptamer are connected to the 5' end and 3' end of the c sequence respectively through the transition sequence TTT, and the first two nucleotides at the 3' end of the a sequence and the b sequence of the DNA vector are independently thiolated; Preferably, the sequence of the CD16a aptamer is: SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Preferably, the sequence of the Act-12c aptamer is: SEQ ID NO: 137: CGGGGAAAGTCACGGGGGGTTTCAGATGTTCTGATCGGTGTGGAG, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Preferably, the sequence of the CTLA-4 aptamer is: SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU, the phosphate backbone between the first 2 nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification; Preferably, the sequence of the GPC1 aptamer is: SEQ ID NO: 189: AACGGAGTGTGGCTAACTCGA, and the phosphate backbone between the last two nucleotides at the 3' end is thiolated; Drug 60): CD16a aptamer-HER3 aptamer-VEGF165 aptamer-DNA vector, wherein, The DNA vector is selected from the third group of nucleic acid vectors described in claim 4, wherein the CD16a aptamer is connected to the 5' end of the a sequence via the transition sequence TTTTT, the HER3 aptamer is connected to the 5' end of the b sequence via the transition sequence TTTTT, and the VEGF165 aptamer is connected to the 5' end of the c sequence via the transition sequence TTTTT, and the first two nucleotides at the 3' end of the a sequence, the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the CD16a aptamer is: SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Preferably, the sequence of the HER3 aptamer is: SEQ ID NO: 197: CAGCGAAAGUUGCGUAUGGGUCACAUCGCAGGCACAUGUCAUCUGGGCG, the phosphate backbone between the first 2 nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification; Preferably, the sequence of the VEGF165 aptamer is: SEQ ID NO: 280: CGGAAUCAGUGAAUGCUUAUACAUCCG, the phosphate backbone between the first 2 nucleotides at the 5' end has a thio modification, C or U has a 2'-F modification, and A or G has a 2'-OME modification; Drug 61): VEGF aptamer-GPC1 aptamer-PD-L1 aptamer-CD16a aptamer-DNA vector, wherein, The DNA vector is selected from the group 11) of the nucleic acid vectors described in claim 4, the VEGF aptamer and the GPC1 aptamer are connected to the 5' end and 3' end of the a sequence respectively through the transition sequence TTTTT, the PD-L1 aptamer and the CD16a aptamer are connected to the 5' end of the b sequence and the 5' end of the c sequence respectively through the transition sequence TTTTT, and the first two nucleotides at the 3' end of the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the VEGF aptamer is: SEQ ID NO: 279: GGTGGGGGTGGACGGGCCGGGTAGA, wherein the phosphate backbone between the first two nucleotides at the 5' end is thiolated; Preferably, the sequence of the GPC1 aptamer is: SEQ ID NO: 189: AACGGAGTGTGGCTAACTCG*A, and the phosphate backbone between the last two nucleotides at the 3' end is thiolated; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Preferably, the sequence of the CD16a aptamer is: SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, and the phosphate backbone between the first 2 nucleotides at the 5' end is thiolated; Drug 62): PD-1 aptamer-PD-L1 aptamer-2*AmiR21-Act-12c aptamer-DNA vector, wherein, The DNA vector is selected from the third group of nucleic acid vectors described in claim 4, wherein the PD-1 aptamer is connected to the 5' end of the a sequence via one AmiR21, the PD-L1 aptamer is connected to the 5' end of the b sequence via another AmiR21, the Act-12c aptamer is connected to the 5' end of the c sequence via a transition sequence TTTTT, and the first two nucleotides at the 3' end of the a sequence, the b sequence, and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the PD-1 aptamer is: SEQ ID NO: 253: AGCGGTGACGGCACAGACGGTACAGTTCCCGTCCCTGCACTACACGTATGCCGCT, and there is a thiolation modification in the phosphate backbone between the first 4 adjacent nucleotides at the 5' end; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, and the phosphate backbone between the first 4 adjacent nucleotides at the 5' end is thiolated; Preferably, the sequence of the Act-12c aptamer is: SEQ ID NO: 137: CGGGGAAAGTCACGGGGGGTTTCAGATGTTCTGATCGGTGTGGAG, and the phosphate backbone between the first 4 adjacent nucleotides at the 5' end is thiolated; Preferably, the sequence of AmiR21 is: GATAAGCT, and there is a thiolation modification in the phosphate backbone between adjacent nucleotides; Drug 63): Her3 aptamer-EGFR siRNA-AS1411 aptamer-Survivin siRNA-Her2 aptamer-DNA vector, wherein, The DNA vector is the 14th group of the nucleic acid vector according to claim 4, wherein the AS1411 aptamer is connected to the 3' end of the a sequence through the transition sequence AAAA, the Her2 aptamer is connected to the 3' end of the b sequence through the transition sequence AAAA, the positive strand of the EGFR siRNA is connected to the 3' end of the c sequence through the transition sequence AAAA; the positive strand of the Survivin siRNA is connected to the 3' end of the b sequence through the transition sequence AAAA, and the first two nucleotides at the 5' end of the a sequence, the b sequence and the c sequence of the DNA vector are independently thiolated; The Her3 aptamer is connected to the antisense strand of the EGFR siRNA through the transition sequence AA, and is connected to the 3' end of the c sequence through the complementary pairing of the antisense strand of the EGFR siRNA and the sense strand of the EGFR siRNA; The Her2 aptamer is connected to the antisense strand of the Survivin siRNA through the transition sequence AA, and is connected to the 3' end of the b sequence through complementary pairing of the antisense strand of the Survivin siRNA and the sense strand of the Survivin siRNA; Preferably, the sequence of the Her3 aptamer is: SEQ ID NO: 197: CAGCGAAAGUUGCGUAUGGGUCACAUCGCAGGCACAUGUCAUCUGGGCG, wherein the phosphate backbone between the first three adjacent nucleotides at the 5' end is thiolated, Preferably, the antisense strand of the EGFR siRNA is: SEQ ID NO: 302: AAUUAGAUAAGACUGCUAAGGCA, and the sense strand is: SEQ ID NO: 82: CCUUAGCAGUCUUAUCUAAUU, and both the antisense strand and the sense strand of the EGFR siRNA are thiolated between the first 3 adjacent nucleotides at the 5' end and between the last 3 adjacent nucleotides at the 3' end; Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, and the phosphate backbone between the last two nucleotides at the 3' end is thiolated; Preferably, the positive strand of the Survivin siRNA is: SEQ ID NO: 303: GCAGGUUCCUUAUCUGUCACA, The antisense strand of the Survivin siRNA is: SEQ ID NO: 300: UGUGACAGAUAAGGAACCUGCAG, wherein, There is a thiolation modification in the phosphate backbone between the first three adjacent nucleotides at the 5' end, and there is a thiolation modification in the phosphate backbone between the last three adjacent nucleotides at the 3' end; _ The sequence of the Her2 aptamer is: SEQ ID NO: 194: AGCCGCGAGGGGAGGGAUAGGGUAGGGCGCGGCU, the phosphate backbone between the first two nucleotides at the 5' end has a thio modification; C or U has a 2'-F modification, and A or G has a 2'-OME modification; Drug 64): Survivin siRNA-TFRA3 aptamer-AS1411 aptamer-3*AmiR-21-DNA vector, wherein, The DNA vector is the 17th group of the nucleic acid vector according to claim 4, wherein the TFRA3 aptamer is connected to the 5' end of the a sequence via one of the AmiR-21s, the FA is connected to the 3' end of the a sequence, the AS1411 aptamer is connected to the 5' end of the b sequence via one of the AmiR-21s, the positive strand of the Survivin siRNA is connected to the 5' end of the c sequence via one of the AmiR-21s, and the antisense strand of the Survivin siRNA is complementary and paired with the positive strand of the Survivin siRNA; Preferably, the sequence of the TFRA3 aptamer is: SEQ ID NO: 262: GCGTGGTCACACGC; Preferably, the sequence of AmiR-21 is: GATAAGCT; Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG; Preferably, the positive strand of the Survivin siRNA is: SEQ ID NO: 304: GCAGGUUCCUUAUCUGUCA, wherein, There is a thiophosphate backbone between the first three adjacent nucleotides at the 5' end. Modification: the phosphate backbone between the last three adjacent nucleotides at the 3' end has a thio modification, and the 7th, 9th to 11th positions from the 5' end have a 2'-F modification, and the rest are 2'-OMe modifications; The antisense strand of the Survivin siRNA is: SEQ ID NO: 305: UGACAGAUAAGGAACCUGCAGUU, with thio modification between the 5' end and the first 3 positions of the 3' end, 2'-F modification at the 2nd, 6th, 8th, 9th, 12th, 14th and 16th positions from the 5' end, and the rest are 2'-OMe modified; Drug 65): AS1411 aptamer-EGFR siRNA-VEGF165 aptamer-PD-L1 aptamer-RNA vector, wherein, The RNA vector is the 16th group of the nucleic acid vector according to claim 4, wherein the VEGF165 aptamer is connected to the 3' end of the a sequence through the transition sequence AA, the PD-L1 aptamer is connected to the 3' end of the b sequence through the transition sequence AA, the sense strand of the EGFR siRNA is connected to the 3' end of the c sequence through the transition sequence AA, the AS1411 aptamer is connected to the 5' end of the antisense strand of the EGFR siRNA through the transition sequence AA, the antisense strand of the EGFR siRNA is complementary to the sense strand of the EGFR siRNA, and the first two nucleotides at the 5' end of the a sequence of the DNA vector are independently thiolated; Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, and the phosphate backbone between the first two nucleotides at the 5' end is thiolated; Preferably, the sense strand of the EGFR siRNA is: SEQ ID NO:82: CCUUAGCAGUCUUAUCUAAUU, and the phosphate backbone between the last three adjacent nucleotides at the 3' end is thiolated; the antisense strand of the EGFR siRNA is: SEQ ID NO:302: AAUUAGAUAAGACUGCUAAGGCA, and the first three positions at the 5' end and the last three positions at the 3' end are both thiolated; Preferably, the sequence of the VEGF165 aptamer is: SEQ ID NO: 280: CGGAAUCAGUGAAUGCUUAUACAUCCG, wherein, C and U have 2'-F modification, A and G have 2'-OME modification, and there is a thio modification on the phosphate backbone between the last 2 nucleotides at the 3' end; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, wherein, C and U have 2'-F modification, A and G have 2'-OME modification, and there is a thio modification on the phosphate backbone between the last 2 nucleotides at the 3' end; Drug 66): CEA aptamer-CD16a-aptamer-Act-12c aptamer-PD-L1 aptamer-DNA vector, wherein, The DNA vector is the 20th group of the nucleic acid vector according to claim 4, wherein the CEA aptamer is connected to the 5' end of the a sequence via a transition sequence AA, the CD16a-aptamer is connected to the 3' end of the a sequence via a transition sequence AA, and the Act-12c aptamer and the PD-L1 aptamer are each connected to the 5' end of the a sequence via a transition sequence AA. AA is connected to the 5' ends of the b sequence and the c sequence, and the first two nucleotides at the 3' ends of the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the CEA aptamer is: SEQ ID NO: 150: TTAACTTATTCGACCATA, the phosphate backbone between the nucleotides 1-2 at the 5' end is thiolated; Preferably, the sequence of the CD16a aptamer is: SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, and the phosphate backbone between the 1st and 2nd nucleotides at the 3' end is thiolated; Preferably, the sequence of the Act-12c aptamer is: SEQ ID NO: 137: CGGGGAAAGTCACGGGGGGTTTCAGATGTTCTGATCGGTGTGGAG, and there is a thiolation modification in the phosphate backbone between the 1st and 2nd nucleotides at the 5' end; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT, and there is a thiolation modification in the phosphate backbone between the 1st and 2nd nucleotides at the 5' end; Drug 67): AS1411 aptamer-TAP siRNA-CD16a aptamer-CTLA-4 aptamer-DNA vector, wherein, The DNA vector is the 14th group of the nucleic acid vector according to claim 4, wherein the CD16a aptamer is connected to the 3' end of the a sequence through the transition sequence AAAA, the CTLA-4 aptamer is connected to the 3' end of the b sequence through the transition sequence AAAA, the sense strand of the TAP siRNA is connected to the 3' end of the c sequence through the transition sequence AAAA, the AS1411 aptamer is connected to the 5' end of the antisense strand of the TAP siRNA through the transition sequence AAA, the antisense strand of the TAP siRNA is complementary to the sense strand of the TAP siRNA, and the first two nucleotides at the 5' end of the a sequence, the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, and there is a thiolation modification on the phosphate backbone between the 1st and 2nd nucleotides at the 5' end; Preferably, the sense strand of the TAP siRNA is: SEQ ID NO: 301: GCUGCACACGGUUCAGAAU, the 1st to 3rd positions at the 5' end and the last 1st to 3rd positions at the 3' end are both thiolated, the 7th and 9th to 11th nucleotides from the 5' end are 2'-F modified, and the remaining nucleotides are 2'-OME modified; The antisense strand of the TAP siRNA is: SEQ ID NO: 109: AUUCUGAACCGUGUGCAGCUU, the 1st to 3rd positions at the 5' end and the 1st to 3rd positions at the end of the 3' end are all thiolated, the 2nd, 6th, 8th, 9th, 12th, 14th and 16th nucleotides from the 5' end are 2'-F modified, and the remaining nucleotides are all 2'-OME modified; Preferably, the sequence of the CD16a aptamer is: SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, with thiolation modification between positions 1-2 at the 5' end and positions 1-2 at the end of the 3' end; Preferably, the sequence of the CTLA-4 aptamer is: SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU, the phosphate backbone between the 1st and 2nd nucleotides at the 3' end has a thio modification, C and U have a 2'-F modification, and A and G have a 2'-OME modification; Drug 68): AS1411 aptamer-TAP siRNA-CD16a aptamer-Act-12c aptamer-DNA vector, wherein, The DNA vector is the 14th group of the nucleic acid vector according to claim 4, wherein the CD16a aptamer is connected to the 3' end of the a sequence through the transition sequence AAAA, the Act-12c aptamer is connected to the 3' end of the b sequence through the transition sequence AAAA, the sense strand of the TAP siRNA is connected to the 3' end of the c sequence through the transition sequence AAAA, the AS1411 aptamer is connected to the 5' end of the antisense strand of the TAP siRNA through the transition sequence AAA, the antisense strand of the TAP siRNA is complementary to the sense strand of the TAP siRNA, and the first two nucleotides at the 5' end of the a sequence, the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, and there is a thiolation modification on the phosphate backbone between the 1st and 2nd nucleotides at the 5' end; Preferably, the sense strand of the TAP siRNA is: SEQ ID NO: 301: GCUGCACACGGUUCAGAAU, the phosphate backbone between adjacent nucleotides at positions 1-3 at the 5' end and positions 1-3 at the 3' end has a thio modification, the 7th and 9-11th nucleotides from the 5' end have a 2'-F modification, and the remaining nucleotides have a 2'-OME modification; The antisense strand of the TAP siRNA is: SEQ ID NO: 109: AUUCUGAACCGUGUGCAGCUU, the phosphate backbone between adjacent nucleotides at positions 1-3 at the 5' end and positions 1-3 at the 3' end has a thio modification, the nucleotides at positions 2, 6, 8, 9, 12, 14, and 16 from the 5' end have a 2'-F modification, and the remaining nucleotides have a 2'-OME modification; Preferably, the sequence of the CD16a aptamer is: SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTG*G, and there is a thiolation modification in the phosphate backbone between the nucleotides at positions 1-2 at the 3' end; Preferably, the sequence of the Act-12c aptamer is: SEQ ID NO: 137: CGGGGAAAGTCACGGGGGGTTTCAGATGTTCTGATCGGTGTGGAG, and the phosphate backbone between the 1st and 2nd nucleotides at the 3' end is thiolated; Drug 69): CD16a aptamer-AS1411 aptamer-TAP siRNA-OX40 aptamer-Act-12c aptamer-DNA vector, wherein, The DNA vector is the 14th group of the nucleic acid vector according to claim 4, so the CD16a aptamer is connected to the 5' end of the a sequence through the transition sequence AA, the sense strand of the TAP siRNA is connected to the 3' end of the a sequence through the transition sequence AA, the AS1411 aptamer is connected to the 5' end of the antisense strand of the TAP siRNA through the transition sequence AAA, the antisense strand of the TAP siRNA is complementary to the sense strand of the TAP siRNA, the OX40 aptamer is connected to the 3' end of the b sequence through the transition sequence AA, the Act-12c aptamer is connected to the 5' end of the c sequence through the transition sequence AAAA, and the first two nucleotides at the 5' end of the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the CD16a aptamer is: SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, and the phosphate backbone between the 1st and 2nd nucleotides at the 5' end is thiolated; Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, and there is a thiolation modification on the phosphate backbone between the 1st and 2nd nucleotides at the 5' end; Preferably, the sense strand of the TAP siRNA is: SEQ ID NO: 301: GCUGCACACGGUUCAGAAU, the phosphate backbone between adjacent nucleotides at positions 1-3 at the 5' end and positions 1-3 at the 3' end is thio-modified, the nucleotides at positions 7, 9, 10 and 11 from the 5' end are 2'-F modified, and the remaining nucleotides are 2'-OME modified; The antisense strand of the TAP siRNA is: SEQ ID NO: 109: AUUCUGAACCGUGUGCAGCUU, the phosphate backbone between adjacent nucleotides at positions 1-3 at the 5' end and positions 1-3 at the 3' end has a thio modification, the nucleotides at positions 2, 6, 8, 9, 12, 14, and 16 from the 5' end have a 2'-F modification, and the remaining nucleotides have a '-OME modification; Preferably, the sequence of the OX40 aptamer is: SEQ ID NO: 228: GGGAGGACGAUGCGGCAGUCUGCAUCGUAGGAAUCGCCACCGUAUACUUUCCCACCAGACGACUCGCUG, the phosphate backbone between the 1st and 2nd nucleotides at the 3' end has a thio modification, C and U have a 2'-F modification, and A and G have a 2'-OMe modification; Preferably, the sequence of the Act-12c aptamer is: SEQ ID NO: 137: CGGGGAAAGTCACGGGGGGTTTCAGATGTTCTGATCGGTGTGGAG, with thiolation modification at positions 1-2 of the 5' end; Drug 70): CTLA-4 aptamer-CD40 aptamer-FAP aptamer-DNA vector, wherein, The DNA vector is group 15) of the nucleic acid vector according to claim 4, wherein the CTLA-4 aptamer is connected to the 5' end of the a sequence via the transition sequence TTTTT, the CD40 aptamer is connected to the 5' end of the b sequence via the transition sequence TTTTT, and the FAP aptamer is connected to the 5' end of the c sequence via the transition sequence TTTTT. The first two nucleotides at the 3' end of the a sequence, the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the CTLA-4 aptamer is: SEQ ID NO: 141: GGUGGAAGAGGGAUGGGCCGACGUGCCGCAU, the phosphate backbone between the 1st and 2nd nucleotides at the 5' end has a thio modification, C and U have a 2'-F modification, and A and G have a 2'-OMe modification; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, wherein the phosphate backbone between the 1st and 2nd nucleotides at the 5' end is thiolated; Preferably, the sequence of the FAP aptamer is: SEQ ID NO: 188: CCGCTCGAGCTAGTCTGACAAAGAGAAACAC, and there is a thiolation modification on the phosphate backbone between the nucleotides 1-2 at the 5' end; Drug 71): VEGF165 aptamer-ASAP1 siRNA-CD24A-2 aptamer-SARS-CoV-2-N48 aptamer-DNA vector, wherein, The DNA vector is the 14th group of the nucleic acid vector according to claim 4, the sense strand of the ASAP1siRNA is connected to the 3' end of the c sequence through a transition sequence AA, the VEGF165 aptamer is connected to the 5' end of the antisense strand of the ASAP1siRNA through a transition sequence AA, the antisense strand of the ASAP1siRNA is complementary to the sense strand of the ASAP1siRNA, the CD24 A-2 aptamer is connected to the 3' end of the b sequence through the transition sequence AA, the SARS-CoV-2-N48 aptamer is connected to the 3' end of the a sequence through the transition sequence AA, and the first two nucleotides at the 5' end of the b sequence and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the VEGF165 aptamer is: SEQ ID NO: 280: CGGAAUCAGUGAAUGCUUAUACAUCCG, the phosphate backbone between the 1st and 2nd nucleotides at the 5' end has a thio modification, C and U have a 2'-F modification, and A and G have a 2'-OME modification; Preferably, the antisense strand of the ASAP1 siRNA is: SEQ ID NO: 65: UGAUAUUAUGGAAGCAAAUUU, the phosphate backbone between the 1st to 3rd nucleotides at the 5' end and the 1st to 3rd nucleotides at the 3' end is thio-modified, the 2nd, 6th, 8th, 9th, 12th, 14th and 16th nucleotides at the 5' end are 2'-F modified, and the rest are 2'-OME modified; The positive strand of the ASAP1 siRNA is: SEQ ID NO: 64: AUUUGCUUCCAUAAUAUCAUU, the phosphate backbone between nucleotides 1-3 at the 5' end and 1-3 at the 3' end has a thio modification, nucleotides 7 and 9-11 at the 5' end have a 2'-F modification, and the rest are 2'-OME modified; Preferably, the sequence of the SARS-CoV-2-N48 aptamer is: SEQ ID NO: 222: GCTGGATGTCGCTTACGACAATATTCCTTAGGGGCACCGCTACATTGACACATCCAGC, and the phosphate backbone between the 1st and 2nd nucleotides at the 3' end is thiolated; Preferably, the sequence of the CD24A-2 aptamer is: SEQ ID NO: 167: ATCCAGAGTGACGCAGCATATGTGGGTGGGTGGGCGGTTATGCTGAGTCAGCCTTGCTTGGACACGGTGGCTTAGT, and there is a thiolation modification in the phosphate backbone between the 1st and 2nd nucleotides at the 5' end; Drug 72): 3*FGF5 aptamer-DNA vector, wherein, The DNA vector is the 15th) group of the nucleic acid vector according to claim 4, wherein the three FGF5 aptamers are each connected to the 5' end of the a sequence, the 5' end of the b sequence, and the 5' end of the c sequence through U, and the first two nucleotides at the 3' end of the a sequence, the b sequence, and the c sequence of the DNA vector are independently thiolated; Preferably, the sequence of the FGF5 aptamer is: SEQ ID NO: 186: GGGCGACCUCUCCGUACUGACCUACAGAGCGACAUACUAGUGUAUCCAGAUCGCCC;, the phosphate backbone between the 1st and 2nd nucleotides at the 5' end has a thio modification, C and U have a 2'-F modification, and A and G have a 2'-OMe modification; Drug 73): AS1411 aptamer-ASAP1 siRNA-VEGF165 aptamer-SARS-CoV-2-N48 aptamer-RNA vector, wherein, The DNA vector is the 21st group of the nucleic acid vector described in claim 4, wherein the VEGF165 aptamer is connected to the 3' end of the a sequence through a transition sequence AA, the SARS-CoV-2-N48 aptamer is connected to the 3' end of the b sequence through the transition sequence AA, the positive strand of the ASAP1 siRNA is connected to the 3' end of the c sequence, the AS1411 aptamer is connected to the 5' end of the antisense strand of the ASAP1 siRNA through the transition sequence AA, and the antisense strand of the ASAP1 siRNA is complementary to the positive strand of the ASAP1 siRNA; the first two nucleotides at the 5' end of the a sequence, the b sequence and the c sequence of the DNA vector are independently thiolated, and A and G in the c sequence are 2'-OME modified, and C and U are 2'-F modified; Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, and the phosphate backbone between the 1st and 2nd nucleotides at the 5' end is thiolated; Preferably, the antisense strand of the ASAP1 siRNA is: SEQ ID NO: 65: UGAUAUUAUGGAAGCAAAUUU, the phosphate backbone between the 1st to 3rd positions of the 5' end and the 1st to 3rd positions of the 3' end has a thio modification, the 2nd, 6th, 8th, 9th, 12th, 14th and 16th positions from the 5' end have a 2'-F modification, and the rest are 2'-OME modifications; The positive strand of the ASAP1 siRNA is: SEQ ID NO: 64: AUUUGCUUCCAUAAUAUCAUU, wherein the phosphate backbone between the 1st to 3rd positions of the 5' end and the 1st to 3rd positions of the 3' end is thiolated; Preferably, the sequence of the VEGF165 aptamer is: SEQ ID NO: 280: CGGAAUCAGUGAAUGCUUAUACAUCCG, C and U have 2'-F modification, A and G have 2'-OMe modification; Preferably, the sequence of the SARS-CoV-2-N48 aptamer is: SEQ ID NO: 222: GCTGGATGTCGCTTACGACAATATTCCTTAGGGGCACCGCTACATTGACACATCCAGC, and the phosphate backbone between the 1st and 2nd nucleotides at the 3' end is thiolated; Drug 74): CpG2006-CD40 aptamer-PD1 aptamer-DNA vector, wherein, The DNA vector is group 6) of the nucleic acid vector according to claim 4, wherein the CpG2006 is connected to the 5' end of the a sequence via a transition sequence, the CD40 aptamer is connected to the 5' end of the b sequence via the transition sequence, and the PD-1 aptamer is connected to the 5' end of the c sequence via the transition sequence; Preferably, the sequence of CpG2006 is: SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and there is a thio modification in the phosphate backbone between adjacent nucleotides; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the 2nd position of the ribose of the first 4 nucleotides at the 5' end has a MOE modification, and the phosphate backbone between the first 5 nucleotides at the 5' end has a thiolation modification; Preferably, the sequence of the PD1 aptamer is: SEQ ID NO: 254: ACCGACAGTGAAGGACTCAGCGAACTCTCAGACTCGGTTC, the 2nd position of the ribose of the first 4 nucleotides at the 5' end has a MOE modification, and the phosphate backbone between the first 5 nucleotides at the 5' end has a thiolation modification; Drug 75): CD24 aptamer-CpG2006 variant-CD40 aptamer-PD-L1 aptamer-DNA vector, wherein, The DNA vector is the 6th group of the nucleic acid vector according to claim 4, wherein the CD24 aptamer is connected to the 5' end of the a sequence via the CpG2006 variant sequence GTCGTT, the CD40 aptamer is connected to the 5' end of the b sequence via the transition sequence TTTTT, and the PD-L1 aptamer is connected to the 5' end of the c sequence via the transition sequence TTTTT; Preferably, the sequence of the CD24 aptamer is: SEQ ID NO: 166: TATGTGGGTGGGTGGGCGGTTATGCTGAGTCAGCCTTGCT, the phosphate backbone of the first 4 nucleotides at the 5' end is thiolated; Preferably, the sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, wherein the phosphate backbone between the first 5 nucleotides at the 5' end is thiolated; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 238: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGG, the ribose of the first 6 nucleotides at the 5' end has a 2'-O-MOE modification; The transition sequence TTTTT is PEG-modified TTTTT; Drug 76): HBsAg aptamer-HBV siRNA-miR-34-PD-L1 aptamer-miR-542-AS1411 aptamer-DNA vector, wherein, The DNA vector is the 24th group of the nucleic acid vector according to claim 4, the sense strand of the HBV siRNA is connected to the 3' end of the a sequence, the HBsAg aptamer is connected to the antisense strand of the HBV siRNA and is located at the 5' end of the antisense strand of the HBV siRNA, the PD-L1 aptamer is connected to the 3' end of the b sequence via the miR-34, and the AS1411 aptamer is connected to the 3' end of the c sequence via the miR-542; Preferably, the sense strand of the HBV siRNA is: SEQ ID NO:88: GGACUUCUCUCAAUUUUCUUU, and the antisense strand is: SEQ ID NO:89: AGAAAAUUGAGAGAAGUCCUU, wherein, The C and U in the sense strand and the antisense strand of the HBV siRNA have 2'-F modification, and the phosphate backbone between the 1st to 3rd nucleotides at the 3' end has phosphothioate modification; Preferably, the sequence of the HBsAg aptamer is: SEQ ID NO: 192: CACAGCGAACAGCGGCGGACATAATAGTGCTTACTACGAC, the phosphate backbone of the first 4 nucleotides at the 5' end is thiolated; Preferably, the sequence of miR-34 is: TGTGACAG; Preferably, the sequence of the PD-L1 aptamer is: SEQ ID NO: 238: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGG, 2'-O-MOE modification exists on the ribose of the 3' nucleotide at the 3' end; Preferably, the sequence of miR-542 is: TGGCAGTGT; Preferably, the sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG, with 2'-O-MOE thio modification on the phosphate backbone between the 4 nucleotides at the 3' end; Drug 77): IL-4Ra aptamer-TIMC-d aptamer-4*miR-126-RNA vector, wherein, The RNA vector is the group 25) of the nucleic acid vector according to claim 4, wherein the IL-4Ra aptamer is directly connected to the 5' end of the a sequence, the TIMC-d aptamer is directly connected to the 5' end of the b sequence, and the four miR-126s are connected in series to the 5' end of the c sequence. The sequence of the IL-4Ra aptamer is: SEQ ID NO: 203: AAAAAGCAACAGGGUGCUCCAUGCGCAUGGAACCUGCGCG, the phosphate backbone of the first 4 nucleotides at the 5' end is thiolated; The sequence of the TIMC-d aptamer is: SEQ ID NO: 272: AAGCAACACUUAGUCGCGAUUGAUACGUGCGCAGUCAU, the phosphate backbone of the first 4 nucleotides at the 5' end is thiolated; The sequence of miR-126 is: UCGUACC, there is a thiolation modification on the phosphate backbone between adjacent nucleotides; Drug 78): CD3-4 aptamer-PD-1 aptamer-BCMA aptamer-DNA vector, wherein, The DNA vector is the group 24) of the nucleic acid vector according to claim 4, wherein the CD3-4 aptamer is connected to the complementary sequence A' of the single-stranded connecting bridge sequence A in the a sequence through the transition sequence TTTTTT, and is connected to the 3' end of the a sequence through the complementary pairing of the complementary sequence A' and the single-stranded connecting bridge sequence A; The PD-1 aptamer is connected to the complementary sequence B' of the single-stranded bridge sequence B in the b sequence through the transition sequence TTTTT, and is connected to the 3' end of the b sequence through the complementary pairing of the complementary sequence B' and the single-stranded bridge sequence B; The BCMA aptamer is connected to the complementary sequence C' of the single-stranded connecting bridge sequence C in the c sequence, and is connected to the 3' end of the c sequence through the complementary pairing of the complementary sequence C' and the single-stranded connecting bridge sequence C; The a sequence is: SEQ ID NO: 15: GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC, wherein, The underlined portion is the single-stranded connecting bridge sequence A; Preferably, the sequence of the complementary sequence A' of the CD3-4 aptamer-transition sequence-single-stranded bridge sequence A is: SEQ ID NO:306: TCTCGGACGCGTGTGGTCGGCCGAGTGGCCCACGGTAGAAGGGTTAGAACTGCTGGTTGGTGAATCTCGCTGCCTGGCCCTAGAGTGTTTTTTGCCACCGTGCTACA; The b sequence in the DNA vector is: SEQ ID NO:16: CCTTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, where, The underlined portion is the single-stranded bridge sequence B; Preferably, the sequence of the complementary sequence B' of the PD-1 aptamer-transition sequence TTTTT-single-stranded bridge sequence B is: SEQ ID NO: 307: ACCGACAGTGAAGGACTCAGCGAACTCTCAGACTCGGTTCTTTTTCACGGCCGCGCCGA; the phosphate backbone between the first 5 nucleotides at the 5' end is thiolated; The c sequence is: SEQ ID NO: 17: GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG, where, The underlined portion is the single-stranded bridge sequence C; Preferably, the complementary sequence C' of the BCMA aptamer-transition sequence U-single-stranded bridge sequence C is: SEQ ID NO: 308: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUACUCAGCAGCAGCAGCA, the underlined portion is the complementary sequence C' of the single-stranded connecting bridge sequence C, the phosphate backbone between the 3 nucleotides at the 3' end is thio-modified, the ribose of the first 4 nucleotides at the 5' end is 2'-O-MOE modified, and the C and U of the remaining nucleotides are 2'F modified; Drug 79): CpG2006-CD38 aptamer-PD-L1 aptamer-DNA vector; wherein, The DNA vector is the 6th group of the nucleic acid vector according to claim 4, wherein the CpG2006 is connected to the 5' end of the a sequence via a transition sequence TTTTT, the CD38 aptamer is connected to the 5' end of the b sequence via a transition sequence TTTTT, and the PD-L1 aptamer is connected to the 5' end of the c sequence via a transition sequence TTTTT. Preferably, the CpG2006-the transition sequence TTTTT-the a sequence is: SEQ ID NO: 309: TCGTCGTTTTGTCGTTTTGTCGTTTTTTTGCGACGCCCACGAGCGTTCCGGGAGAGGAGC, and the phosphate backbone of the adjacent nucleotides of the CpG2006 has a thio modification; Preferably, the CD38 aptamer-the transition sequence TTTTT-the b sequence is: SEQ ID NO: 310: TACGTGAATCTCGTACGATACTCTGTAAGCGTTTTTTGCTCCTCTCCCGGTTCG CCGCGAGCCGCG, the ribose of the first 3 nucleotides at the 5′ end has a 2′-O-MOE modification; Preferably, the PD-L1 aptamer-the transition sequence TTTTT-the c sequence is: SEQ ID NO: 311: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGGTTTTTCGCGGCTC GCGGCCATAGCCGTGGGCGTCGC, the ribose of the first 6 nucleotides at the 5′ end has a 2′-O-MOE modification; Drug 80): CD20 aptamer-CpG-BYZD-CD38 aptamer-miR-34-CD3 aptamer-DNA vector; wherein, The DNA vector is the 6th group of the nucleic acid vector according to claim 4, wherein the CD20 aptamer is connected to the 5' end of the a sequence through the CpG-BYZDAGCGAA, the CD38 aptamer is connected to the 5' end of the b sequence through the miR-34, and the CD3 aptamer is connected to the 5' end of the c sequence through the transition sequence TTTTT. Preferably, the CD20 aptamer-the CpG-BYZD-the a sequence is: SEQ ID NO: 312: TCGTGTGTAGTGTGTCTGTTTTTTATCTTCTTTTATCTACTCTTAGGGATTTGGGCGGAGCGAAGCGACGCCCACGAGCGTTCCGGGAGAGGAGC, SEQ ID NO: 165: TCGTGTGTAGTGTGTCTGTTTTTTATCTTCTTTTATCTACTCTTAGGGATTTGGGCGG_ is the CD20 aptamer, AGCGAA is the CpG-BYZD, and the phosphate backbone between the first 4 nucleotides at the 5' end is thiolated; Preferably, the CD38 aptamer-the miR-34-the b sequence is: SEQ ID NO: 313: TACGTGAATCTCGTACGATACTCTGTAAGCGTTGTGACAGGCTCCTCTCCCGGTTCGCCGCGAGCCGCG, there is a 2'-O-MOE modification on the ribose of the first 3 nucleotides at the 5' end, TGTGACAG is the miR-34, before TGTGACAG is the CD38 aptamer, and after TGTGACAG is the b sequence; Preferably, the CD3 aptamer-the transition sequence TTTTT-the c sequence is: SEQ ID NO: 314: GCCGCGGGGTGGGTCTAGTGTGGATGTTTAGGGGGCGGCTTTTTCGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, and there is 2'-O-MOE modification on the ribose of the first 4 nucleotides at the 5' end; Drug 81): CpG2006-CD38 aptamer-miR-126-PD-L1 aptamer-DNA vector; wherein, The DNA vector is group 6) of the nucleic acid vector according to claim 4, wherein the CpG2006 is connected to the 5' end of the a sequence via the transition sequence TTTTT, the CD38 aptamer is connected to the 5' end of the b sequence via the miR-126, and the PD-L1 aptamer is connected to the 5' end of the c sequence via the transition sequence TTTTT. Preferably, the CpG2006-the transition sequence TTTTT-the a sequence is: SEQ ID NO: 309: TCGTCGTTTTGTCGTTTTGTCGTTTTTTTGCGACGCCCACGAGCGTTCCGGGAGAGGAGC, there is a thiolation modification on the phosphate backbone between adjacent nucleotides of the CpG2006, and there is a thiolation modification on the phosphate backbone between the two nucleotides at the 3' end of the a sequence; Preferably, the CD38 aptamer-the miR-126-the b sequence is: SEQ ID NO: 315: TACGTGAATCTCGTACGATACTCTGTAAGCGTUCGUACCGGCTCCTCTCCCGGTTCGCCGCGAGCCGCG, wherein, The sequence of the CD38 aptamer is SEQ ID NO: 170: TACGTGAATCTCGTACGATACTCTGTAAGCGT, and the ribose of the first three nucleotides at the 5' end has a 2'-O-MOE modification; UCGUACCG is the sequence of the miR-126, and the ribose of each nucleotide has a 2'-O-MOE modification; Preferably, the PD-L1 aptamer-the transition sequence TTTTT-the c sequence is: SEQ ID NO: 311: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGGTTTTTCGCGGCTCG CGGCCATAGCCGTGGGCGTCGC, the ribose of the first 6 nucleotides at the 5' end of the PD-L1 aptamer has a 2'-O-MOE modification; Drug 82): BCMA aptamer-miR-126-CD38 aptamer-miR-122-CD3 aptamer-miR-34-DNA vector; wherein, The DNA vector is the nucleic acid vector of group 6) according to claim 4, wherein the BCMA is suitable for The ligand is connected to the 5' end of the a sequence through the transition sequence U and the miR-126, the CD38 aptamer is connected to the 5' end of the b sequence through the miR-122, and the CD3 aptamer is connected to the 5' end of the c sequence through the miR-34; Preferably, the BCMA aptamer-transition sequence U-the miR-126-the a sequence is: SEQ ID NO: 316: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUACUCGTACCGGCGACGCCCACGAGCGTTCCGGGAGAGGAGC, where, CGTACCG is the sequence of miR-126, the sequence of the BCMA aptamer is before CGTACCG, the a sequence is after CGTACCG, the ribose of the first 4 nucleotides at the 5' end of the sequence of the BCMA aptamer has 2'-O-MOE, and the C and U in the remaining positions have 2'F modification; Preferably, the CD38 aptamer-the miR-122-the b sequence is: SEQ ID NO: 317: TmAmCmGTGAATCTCGTACGATACTCTGTAAGCGTGGAAGTGTGCTCCTCTCCCGGTTCGCCGCGAGCCGCG, the ribose of the first 3 nucleotides at the 5' end has a 2'-O-MOE modification, GGAAGTGT is the sequence of the miR-122, the sequence before GGAAGTGT is the sequence of the CD38 aptamer, and the sequence after GGAAGTGT is the b sequence, Preferably, the CD3 aptamer-the miR-34-the c sequence is: SEQ ID NO: 318: AmGmCmCmGCGGGGTGGGTCTAGTGTGGATGTTTAGGGGGCGGCTTGTGACAGCGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the ribose of the first 4 nucleotides at the 5' end has a 2'-O-MOE modification, TGTGACA is the sequence of the miR-34, the sequence before TGTGACA is the sequence of the CD3 aptamer, and the sequence after TGTGACA is the c sequence; Drug 83): GPC3 aptamer-AmiR-21-CD38 aptamer-miR-122-PD-L1 aptamer-miR-34-DNA vector; wherein, The DNA vector is the 6th group of the nucleic acid vector according to claim 4, the GPC3 aptamer is connected to the 5' end of the a sequence through the AmiR-21, the CD38 aptamer is connected to the 5' end of the b sequence through the miR-122, and the PD-L1 aptamer is connected to the 5' end of the c sequence through the miR-34; Preferably, the GPC3 aptamer-the AmiR-21-the a sequence is: SEQ ID NO: 319: TAACGCTGACCTTAGCTGCATGGCTTTACATGTTCCAGATAAGCTGCGACGCCCACGAGCGTTCCGGGAGAGGAGC, the phosphate backbone between the first 4 nucleotides at the 5' end has a thiolation modification, GATAAGCT is the sequence of the AmiR-21, the sequence before GATAAGCT is the sequence of the GPC3 aptamer, and the sequence after GATAAGCT is the a sequence; Preferably, the CD38 aptamer-the miR-122-the b sequence is: SEQ ID NO: 317: TACGTGAATCTCGTACGATACTCTGTAAGCGTGGAAGTGTGCTCCTCTCCCGGTTCGCCGCGAGCCGCG, the phosphate backbone between the first 4 nucleotides at the 5' end has a thiolation modification; GGAAGTGT is The sequence of miR-122, the sequence before GGAAGTGT is the sequence of the CD38 aptamer, and the sequence after GGAAGTGT is the b sequence; Preferably, the PD-L1 aptamer-the miR-34-the c sequence is: SEQ ID NO: 320: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGGTGTGACAGCGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the ribose of the first 6 nucleotides at the 5' end has a 2'-O-MOE modification; TGTGACAAG is the sequence of the miR-34, the sequence before TGTGACAAG is the sequence of the PD-L1 aptamer, and the sequence after TGTGACAAG is the c sequence; Drug 84): CpG2006-VEGF165 aptamer-miR-122-PD-L1 aptamer-DNA vector; wherein, The DNA vector is group 6) of the nucleic acid vector according to claim 4, wherein the CpG2006 is connected to the 5' end of the a sequence via the transition sequence TTTTT, the VEGF165 aptamer is connected to the 5' end of the b sequence via the miR-122, and the PD-L1 aptamer is connected to the 5' end of the c sequence via the transition sequence TTTTT; Preferably, the CpG2006-the transition sequence TTTTT-the a sequence is: SEQ ID NO: 309: TCGTCGTTTTGTCGTTTTGTCGTTTTTTTGCGACGCCCACGAGCGTTCCGGGAGAGGAGC; the phosphate backbone between adjacent nucleotides of the CpG2006 has a thio modification; Preferably, the VEGF165 aptamer-the miR-122-the b sequence is: SEQ ID NO: 321: CGGAAUCAGUGAAUGCUUAUACAUCCGGGAAGTGTGCTCCTCTCCCGGTTCGCCGCGAGCCGCG, the ribose of the first 4 nucleotides at the 5' end has a 2'-O-MOE modification, and the C and U in the remaining RNA have a 2'F modification; GGAAGTGT is the sequence of the miR-122, the sequence before GGAAGTGT is the sequence of the VEGF165 aptamer, and the sequence after GGAAGTGT is the b sequence; Preferably, the PD-L1 aptamer-the transition sequence TTTTT-the c sequence is: SEQ ID NO: 311: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGGTTTTTCGCGGCTC GCGGCCATAGCCGTGGGCGTCGC, the ribose of the first 6 nucleotides at the 5′ end has a 2′-O-MOE modification; Drug 85): CpG2006-HBsAg aptamer-miR-122-PD-L1 aptamer-DNA vector; wherein, The DNA vector is group 6) of the nucleic acid vector according to claim 4, wherein the CpG2006 is connected to the 5' end of the a sequence via the transition sequence TTTTT, the HBsAg aptamer is connected to the 5' end of the b sequence via the miR-122, and the PD-L1 aptamer is connected to the 5' end of the c sequence via the transition sequence TTTTT; Preferably, the CpG2006-the transition sequence TTTTT-the a sequence is: SEQ ID NO: 309: TCGTCGTTTTGTCGTTTTGTCGTTTTTTTGCGACGCCCACGAGCGTTCCGGGAGAGGAGC; the phosphate backbone between adjacent nucleotides of the CpG2006 has a thio modification; Preferably, the HBsAg aptamer-the miR-122-the b sequence is: SEQ ID NO: 322: CACAGCGAACAGCGGCGGACATAATAGTGCTTACTACGACGGAAGTGTGCTCCTCTCCCGGTTCGCCGCGAGCCGCG, the phosphate backbone between the first 4 nucleotides at the 5' end has a thio modification; GGAAGTGT is the sequence of the miR-122, the sequence before GGAAGTGT is the sequence of the HBsAg aptamer, and the sequence after GGAAGTGT is the b sequence; Preferably, the PD-L1 aptamer-the transition sequence TTTTT-the c sequence is: SEQ ID NO: 311: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGGTTTTTCGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the ribose of the first 6 nucleotides at the 5' end has a 2'-O-MOE modification; Drug 86): ASO-GSK836-HBsAg aptamer-miR-122-PD-L1 aptamer-DNA vector; wherein, The DNA vector is the 6th group of the nucleic acid vector according to claim 4, wherein the ASO-GSK836 is connected to the 5' end of the a sequence via the transition sequence TTTTT, the HBsAg aptamer is connected to the 5' end of the b sequence via the miR-122, and the PD-L1 aptamer is connected to the 5' end of the c sequence via the transition sequence TTTTT; Preferably, the ASO-GSK836-the transition sequence TTTTT-the a sequence is: SEQ ID NO: 323: GCAGAGGTGAAGCGAAGTCGTTTTTGCGACGCCCACGAGCGTTCCGGGAGAG GAGC, the phosphate backbone between the adjacent nucleotides at the first 6 nucleotides of the 5' end has a thiolation modification; Preferably, the HBsAg aptamer-the miR-122-the b sequence is: SEQ ID NO: 322: CACAGCGAACAGCGGCGGACATAATAGTGCTTACTACGACGGAAGTGTGCTCCTCTCCCGGTTCGCCGCGAGCCGCG, the phosphate backbone between the first 4 nucleotides at the 5' end has a thio modification; GGAAGTGT is the sequence of the miR-122, the sequence before GGAAGTGT is the sequence of the HBsAg aptamer, and the sequence after GGAAGTGT is the b sequence; Preferably, the PD-L1 aptamer-the transition sequence TTTTT-the c sequence is: SEQ ID NO: 311: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGGTTTTTCGCGGCTCG CGGCCATAGCCGTGGGCGTCGC, the ribose of the first 6 nucleotides at the 5′ end has a 2′-O-MOE modification; Drug 87): BCMA aptamer-CD38 aptamer-miR-126-PD-L1 aptamer-miR-34-DNA vector; wherein, The DNA vector is group 6) of the nucleic acid vector according to claim 4, wherein the BCMA aptamer is connected to the 5' end of the a sequence via the transition sequence UU, the CD38 aptamer is connected to the 5' end of the b sequence via the miR-126, and the PD-L1 aptamer is connected to the 5' end of the c sequence via the miR-34; Preferably, the BCMA aptamer-transition sequence UU-the a sequence is: SEQ ID NO: 324: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUACUUGC GACGCCCACGAGCGTTCCGGGAGAGGAGC, among which, SEQ ID NO: 140: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUAC is the BCMA aptamer in RNA form, all nucleotides of the RNA have 2'-F modification, and the rest is the a sequence, Preferably, the CD38 aptamer-the miR-126-the b sequence is: SEQ ID NO: 325: TACGTGAATCTCGTACGATACTCTGTAAGCGTGTCGTTGCTCCTCTCCCGGTTCGCCGCGAGCCGCG, the phosphate backbone between the first 4 nucleotides at the 5' end has a thio modification, GTCGTT is the sequence of the miR-126, the sequence before GTCGTT is the CD38 aptamer, and the sequence after GTCGTT is the b sequence; Preferably, the PD-L1 aptamer-the miR-34-the c sequence is: SEQ ID NO: 320: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGGTGTGACAGCGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the ribose of the first 6 nucleotides at the 5' end has a 2'-O-MOE modification, TGTGACAG is the sequence of the miR-34, the sequence before TGTGACAAG is the sequence of the PD-L1 aptamer, and the sequence after TGTGACAAG is the c sequence; Drug 88): AS1411 aptamer-FGF2 aptamer-3*AmiR-21-DNA vector; the AS1411 aptamer is connected to the 5' end of the DNA vector a sequence through the transition sequence TTTTT, the FGF2 aptamer is connected to the 5' end of the DNA vector b sequence through the transition base U, and the three AmiR-21s are directly connected in series to the 5' end of the DNA vector c sequence, Preferably, the AS1411 aptamer-the transition sequence TTTTT-the a sequence is: SEQ ID NO: 326: GGTGGTGGTGGTTGTGGTGGTGGTGGTTTTTGCGCCCACGAGCGTTCCGGGAG AGC; Preferably, the FGF2 aptamer-the transition base U-the b sequence is: SEQ ID NO: 327: GGGAUACUAGGGCAUUAAUGUUACCAGUGUAGUCCCUCCCUGCTCTCCCGGTTCGCCGCCAGCCGCC, wherein, SEQ ID NO: 183: GGGAUACUAGGGCAUUAAUGUUACCAGUGUAGUCCC is the FGF2 aptamer in RNA form, the C and U bases in the RNA have 2'-F modifications, and the remainder is the b sequence; Preferably, the 3*AmiR-21-c sequence is: SEQ ID NO: 328: GATAAGCTGATAAGCTGATAAGCTGGCGGCAGGCGGCCATAGCCGTGGGCGC, GATAAGCT is the sequence of the AmiR-21, and the phosphate backbone of adjacent nucleotides has thio modification; Drug 89): HBsAg aptamer-CD40 aptamer-PD-L1 aptamer-DNA vector, wherein the HBsAg aptamer is connected to the 5' end of the DNA vector a sequence via a transition sequence TTTTT, and the CD40 aptamer is connected to the 5' end of the DNA vector a sequence via a transition sequence TTTTT. The transition sequence TTTTT is connected to the 5' end of the DNA vector b sequence, and the PD-L1 adaptor is connected to the 5' end of the DNA vector c sequence through the transition sequence TTTTT. Preferably, the HBsAg aptamer-the transition sequence TTTTT-the a sequence is: SEQ ID NO: 329: CACAGCGAACAGCGCGGGACATAATAGTGCTTACTACGACTTTTTGCGACGCC CACGAGCGTTCCGGGAGAGGAGC, the phosphate backbone of the first 4 nucleotides at the 5' end is thio-modified, the sequence before the transition sequence TTTTT is the sequence of the HBsAg aptamer, and the sequence after the transition sequence TTTTT is the a sequence; Preferably, the CD40 aptamer-the transition sequence TTTTT-the b sequence is: SEQ ID NO: 330: CCAACGAGTAGGCGATAGCGCGTGGTTTTGCTCCTCTCCCGGTTCGCCGCGA GCCGCG, the phosphate backbones between the first 3 nucleotides at the 5' end and the first 3 nucleotides at the 3' end are both thiolated, the sequence before the transition sequence TTTTT is the sequence of the CD40 aptamer, and the sequence after the transition sequence TTTTT is the b sequence; Preferably, the PD-L1 aptamer-the transition sequence TTTTT-the c sequence is: SEQ ID NO: 331: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGTTTTTTCCGG GCTCGCGGCCATAGCCGTGGGCGTCGC, the phosphate backbone between the first 3 nucleotides at the 5' end and the first 3 nucleotides at the 3' end has a thio modification, the sequence before the transition sequence TTTTT is the sequence of the PD-L1 aptamer, and the sequence after the transition sequence TTTTT is the c sequence; Drug 90): HBsAg aptamer-CD40 aptamer-PD-L1 aptamer-DNA vector, compared with drug 89), except for the sequence of PD-L1 aptamer, the rest are the same, among which, The PD-L1 aptamer-the transition sequence TTTTT-the c sequence is: SEQ ID NO: 311: AACAACGTATAACAATGCCCACGTCACCAGAGTACTATGGTTTTTCGCGGCTCGCGGCCATAGCCGTGGGCGTCGC, the ribose of the first 6 nucleotides at the 5' end has a 2'-O-MOE modification, the sequence before the transition sequence TTTTT is the sequence of the PD-L1 aptamer, and the sequence after the transition sequence TTTTT is the c sequence; Drug 91): BCMA aptamer-CD38 aptamer-CpG-BYZD-CD19 aptamer-AmiR-21-DNA vector, wherein, The a sequence, b sequence and c sequence of the DNA vector are as follows: The a sequence is: SEQ ID NO: 15: GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC, where, Underlined part is the single-stranded connecting bridge sequence A; The b sequence is: SEQ ID NO: 16: CCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, where, The underlined part is a single strand Connecting bridge sequence B; The c sequence is: SEQ ID NO: 17: GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG, where, The underlined part is Single-stranded connecting bridge sequence C; The CD38 aptamer is connected to the complementary sequence A' of the single-stranded bridge sequence A through the transition sequence TT and CpG-BYZD, and the complementary sequence A' is complementary to the single-stranded bridge sequence A, wherein: The CD38 aptamer-CpG-BYZD-the complementary sequence A' is: SEQ ID NO: 332: TACGTGAATCTCGTACGATACTCTGTAAGCGTTTAGCGAAGCCACCGTGCTACA, wherein, SEQ ID NO: 170: TACGTGAATCTCGTACGATACTCTGTAAGCGT is the CD38 aptamer, and the phosphate backbone between the first 4 nucleotides at the 5' end has a thio modification; SEQ ID NO: 8: GCCACCGTGCTACA is the complementary sequence A', TT is the transition sequence, and AGCGAA is the CpG-BYZD; The CD19 aptamer is connected to the 5' end of the complementary sequence B' of the single-stranded bridge sequence B via the AmiR-21, and the complementary sequence B' is complementary to the single-stranded bridge sequence B, wherein: The CD19 aptamer-the AmiR-21-the complementary sequence B' is: SEQ ID NO: 333: UGAGCCUGUUCGACAGGAGGCUCAGAUAAGCUCACGGCCGCGCCGA, wherein, SEQ ID NO: 160: UGAGCCUGUUCGACAGGAGGCUCA is the sequence of the CD19 aptamer, and the C and U-bases have 2'F modifications; GAUAAGCU is the sequence of the AmiR-21, and the C and U have 2'F modifications; SEQ ID NO: 10: CACGGCCGCGCCGA is the complementary sequence B'; The BCMA aptamer is connected to the 5' end of the complementary sequence C' of the single-stranded bridge sequence C via the transition sequence AA, and the complementary sequence C' is complementary to the single-stranded bridge sequence C, wherein: The BCMA aptamer-the transition sequence AA-the complementary sequence C' is: SEQ ID NO: 334: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUACAACAGCAGCAGCAGCA, wherein, SEQ ID NO:12: CAGCAGCAGCAGCA is the complementary sequence C', SEQ ID NO:140: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUAC is the sequence of the BCMA aptamer, and the C and U bases in the RNA sequence of the BCMA aptamer have 2'F modification; Drug 92): BCMA aptamer-CD38 aptamer-CD19 aptamer-AmiR-21-DNA vector, wherein, The a sequence, b sequence and c sequence of the DNA vector are as follows: The a sequence is: SEQ ID NO: 15: GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC, where, Underlined part is a single-stranded connecting bridge sequence A; the b sequence is: SEQ ID NO: 16: CCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, where, The underlined part is a single strand The connecting bridge sequence B; the c sequence is: SEQ ID NO: 17: GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG, where, The underlined part is Single-stranded connecting bridge sequence C; The CD38 aptamer is connected to the complementary sequence A' of the single-stranded bridge sequence A via a transition sequence TTTTT, and the complementary sequence A' is complementary to the single-stranded bridge sequence A, wherein: The sequence of the CD38 aptamer-the transition sequence TTTTT-the complementary sequence A' is: SEQ ID NO: 335: TACGTGAATCTCGTACGATACTCTGTAAGCGTTTTTTGCCACCGTGCTACA, SEQ ID NO: 170: TACGTGAATCTCGTACGATACTCTGTAAGCGT is the sequence of the CD38 aptamer, and the phosphate backbone between the first 4 nucleotides at the 5' end has a thio modification; SEQ ID NO: 8: GCCACCGTGCTACA is the complementary sequence A' of the single-stranded connecting bridge sequence A; The CD19 aptamer is connected to the complementary sequence B' of the single-stranded bridge sequence B through the AmiR-21, and the complementary sequence B' is complementary to the single-stranded bridge sequence B, wherein The sequence of the CD19 aptamer-the AmiR-21-the complementary sequence B' is: SEQ ID NO: 333: UGAGCCCUGUUCGACAGGAGGCUCAGAUAAGCUCACGGCCGCGCCGA, wherein, SEQ ID NO: 160: UGAGCCUGUUCGACAGGAGGCUCA is the sequence of the CD19 aptamer, C and U have 2'F modifications; GAUAAGCU is the sequence of the AmiR-21, C and U have 2'F modifications; SEQ ID NO: 10: CACGGCCGCGCCGA is the complementary sequence B'; The BCMA aptamer is connected to the 5' end of the complementary sequence C' of the single-stranded bridge sequence C via the transition sequence AA, and the complementary sequence C' is complementary to the single-stranded bridge sequence C, wherein: The BCMA aptamer-the transition sequence AA-the complementary sequence C' is: SEQ ID NO: 334: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUACAACAGCAGCAGCAGCA, wherein, SEQ ID NO:12: CAGCAGCAGCAGCA is the complementary sequence C', SEQ ID NO:140: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUAC is the sequence of the BCMA aptamer, and the C and U bases in the RNA sequence of the BCMA aptamer have 2'F modification; Drug 93): CpG2006-CD38 aptamer-PD-L1 aptamer-DNA vector, wherein, The a sequence, b sequence and c sequence of the DNA vector are as follows: The a sequence is: SEQ ID NO: 15: GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC, where, Underlined part is the single-stranded connecting bridge sequence A; The b sequence is: SEQ ID NO: 16: CCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, where, The underlined part is a single strand Connecting bridge sequence B; The c sequence is: SEQ ID NO: 17: GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG, where, The underlined part is Single-stranded connecting bridge sequence C; The CD38 aptamer is connected to the complementary sequence A' of the single-stranded bridge sequence A through the transition sequence TTTTT, and the complementary sequence A' is complementary to the single-stranded bridge sequence A and connected to the 3' end of the a sequence, wherein: The sequence of the CD38 aptamer-the transition sequence TTTTT-the complementary sequence A' is: SEQ ID NO: 335: TACGTGAATCTCGTACGATACTCTGTAAGCGTTTTTTGCCACCGTGCTACA, SEQ ID NO: 170: TACGTGAATCTCGTACGATACTCTGTAAGCGT is the sequence of the CD38 aptamer, and the phosphate backbone between the first 4 nucleotides at the 5' end has a thiolation modification; SEQ ID NO: 8: GCCACCGTGCTACA is the complementary sequence A' of the single-stranded connecting bridge sequence A; The PD-L1 aptamer is connected to the 5' end of the complementary sequence B' of the single-stranded bridge sequence B through the transition sequence TTTTT, and the PD-L1 aptamer is connected to the 3' end of the b sequence through the complementary pairing of the complementary sequence B' and the single-stranded bridge sequence B. The CpG2006 is connected to the 5' end of the complementary sequence C' of the single-stranded bridge C sequence through the transition sequence TTTTT, and the CpG2006 is connected to the 3' end of the c sequence through the complementary pairing between the complementary sequence C' and the single-stranded bridge C sequence; The sequence of the PD-L1 aptamer-the transition sequence TTTTT-the complementary sequence B' is: SEQ ID NO: 336: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGTTTTTTCACG GCCGCGCCGA, the phosphate backbone between the first 4 adjacent nucleotides at the 5' end is thiolated; SEQ ID NO:241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT is the sequence of the PD-L1 aptamer, and SEQ ID NO:10: CACGGCCGCGCCGA is the complementary sequence B'; The sequence of the CpG2006-the transition sequence TTTTT-the complementary sequence C' is: SEQ ID NO: 337: TCGTCGTTTTGTCGTTTTGTCGTTTTTTTCAGCAGCAGCAGCA, wherein, SEQ ID NO:57: TCGTCGTTTTGTCGTTTTGTCGTT is the sequence of CpG2006, in which the phosphate backbone between adjacent nucleotides in the sequence of CpG2006 is thiolated; SEQ ID NO:12: CAGCAGCAGCAGCA is the complementary sequence C'; Drug 94): BCMA aptamer-CD38 aptamer-CpG-BYZD-PD-L1 aptamer-DNA vector, wherein, The a sequence, b sequence and c sequence of the DNA vector are as follows: The a sequence is: SEQ ID NO: 15: GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC, where, Underlined part is the single-stranded connecting bridge sequence A; The b sequence is: SEQ ID NO: 16: CCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, where, The underlined part is a single strand Connecting bridge sequence B; The c sequence is: SEQ ID NO: 17: GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG, where, The underlined part is Single-stranded connecting bridge sequence C; The CD38 aptamer is connected to the complementary sequence A' of the single-stranded bridge sequence A through CpG-BYZD, and the complementary sequence A' is complementary to the single-stranded bridge sequence A and connected to the 3' end of the a sequence, wherein: The sequence of the CD38 aptamer-the CpG-BYZD-the complementary sequence A' is: SEQ ID NO:332: TACGTGAATCTCGTACGATACTCTGTAAGCGTTTAGCGAAGCCACCGTGCTACA , SEQ ID NO: 170: TACGTGAATCTCGTACGATACTCTGTAAGCGT is the sequence of the CD38 aptamer, and the phosphate backbone between the first 4 nucleotides at the 5' end has a thio modification; SEQ ID NO: 8: GCCACCGTGCTACA is the complementary sequence A' of the single-stranded bridge sequence A; TT is a transition sequence, and AGCGAA is the CpG-BYZD; The PD-L1 aptamer is connected to the 5' end of the complementary sequence B' of the single-stranded bridge sequence B through the transition sequence TTTTT, and the PD-L1 aptamer is connected to the 3' end of the b sequence through the complementary pairing of the complementary sequence B' and the single-stranded bridge sequence B. The BCMA aptamer is directly connected to the 5' end of the complementary sequence C' of the single-stranded bridge C sequence, and the BCMA aptamer is connected to the 3' end of the C sequence through the complementary pairing between the complementary sequence C' and the single-stranded bridge C sequence; The sequence of the PD-L1 aptamer-the transition sequence TTTTT-the complementary sequence B' is: SEQ ID NO: 336: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGTTTTTTCACG GCCGCGCCGA, the phosphate backbone between the first 4 adjacent nucleotides at the 5' end is thiolated; SEQ ID NO:241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT is the sequence of the PD-L1 aptamer, and SEQ ID NO:10: CACGGCCGCGCCGA is the complementary sequence B'; The sequence of the BCMA aptamer-the transition sequence AA-the complementary sequence C' is: SEQ ID NO: 334: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUACA ACAGCAGCAGCAGCA, among which, SEQ ID NO:140: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUAC is the BCMA aptamer, and the C and U bases in the RNA sequence of the BCMA aptamer have 2'F modification; SEQ ID NO: 12: CAGCAGCAGCAGCA is the complementary sequence C'; Drug 95): BCMA aptamer-CD40 aptamer-PD-L1 aptamer-DNA vector, wherein, The a sequence, b sequence and c sequence of the DNA vector are as follows: The a sequence is: SEQ ID NO: 15: GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC, where, Underlined part is the single-stranded connecting bridge sequence A; The b sequence is: SEQ ID NO: 16: CCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, where, The underlined part is a single strand Connecting bridge sequence B; The c sequence is: SEQ ID NO: 17: GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG, where, The underlined part is Single-stranded connecting bridge sequence C; The CD40 aptamer is connected to the complementary sequence A' of the single-stranded bridge sequence A through the transition sequence TTTTT, and the complementary sequence A' is complementary to the single-stranded bridge sequence A and connected to the 3' end of the a sequence, wherein: The sequence of the CD40 aptamer-the transition sequence TTTTT-the complementary sequence A' is: SEQ ID NO:338: GCCAACGAGTAGGCGATAGCGCGTGGCTTTTTGCCACCGTGCTACA, among which, SEQ ID NO: 156: GCCAACGAGTAGGCGATAGCGCGTGGC is the CD40 aptamer, and the phosphate backbone between the first 4 nucleotides at the 5' end has a thiolation modification; SEQ ID NO: 8: GCCACCGTGCTACA is the complementary sequence A' The PD-L1 aptamer is connected to the 5' end of the complementary sequence B' of the single-stranded bridge sequence B through the transition sequence TTTTT, and the PD-L1 aptamer is connected to the 3' end of the b sequence through the complementary pairing of the complementary sequence B' and the single-stranded bridge sequence B. The BCMA aptamer is directly connected to the 5' end of the complementary sequence C' of the single-stranded bridge C sequence, and the BCMA aptamer is connected to the 3' end of the C sequence through the complementary pairing between the complementary sequence C' and the single-stranded bridge C sequence; The sequence of the PD-L1 aptamer-the transition sequence TTTTT-the complementary sequence B' is: SEQ ID NO: 336: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGTTTTTTCACG GCCGCGCCGA, the phosphate backbone between the first 4 adjacent nucleotides at the 5' end is thiolated; SEQ ID NO:241: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGT is the sequence of the PD-L1 aptamer, SEQ ID NO:10: CACGGCCGCGCCGA is the complementary sequence B'; The sequence of the BCMA aptamer-the transition sequence AA-the complementary sequence C' is: SEQ ID NO:334: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUACA ACAGCAGCAGCAGCA, among which, SEQ ID NO: 140: AGUGCAAGACGUUCGCAGAUUAGCGAAAAGAGGGUCUCAUUGACUAGUAC is the BCMA aptamer, and the C and U bases in the RNA sequence of the BCMA aptamer have 2'F modifications; SEQ ID NO: 12: CAGCAGCAGCAGCA is the complementary sequence C'; Drug 96): AmiR-21-AS1411 aptamer-CD40 aptamer-2*biotin-DNA vector, wherein, The DNA vector is selected from the group 1) of the nucleic acid vectors described in claim 4, the AmiR-21 is connected to the 5' end of the a sequence, the AS1411 aptamer is connected to the 5' end of the b sequence via the transition sequence TTTTT, the CD40 aptamer is connected to the 5' end of the c sequence via the transition sequence TTTTT, one of the biotins is modified at the 3' end of the a sequence, and the other one of the biotins is modified at the 3' end of the c sequence; The sequence of AmiR21 is GATAAGCT, and each nucleotide has a locked nucleic acid modification; The sequence of the AS1411 aptamer is: SEQ ID NO: 131: GGTGGTGGTGGTTGTGGTGGTGGTGG; The sequence of the CD40 aptamer is: SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG; Drug 97): 2*AmiR-21-4*biotin-DNA vector; in, The DNA vector is the 11th group of the nucleic acid vector according to claim 4, wherein two AmiR21s are directly connected to the 5' ends of the a sequence and the c sequence, respectively, and four biotins are connected to the 3' end of the a sequence, the 5' end and the 3' end of the b sequence, and the 3' end of the c sequence, respectively. Preferably, the sequence of AmiR-21 is GATAAGCT, wherein each nucleotide is modified with a locked nucleic acid; Drug 98): TTA1 aptamer-epirubicin-4*biotin-DNA vector; The DNA vector is group 13) of the nucleic acid vector according to claim 4, the four AmiR21s are directly connected to the 5' end and 3' end of the a sequence and the c sequence, respectively, the TTA1 aptamer is connected to the 5' end of the b sequence through a transition sequence, and the epirubicin is inserted between the GC adjacent base pairs of the nucleic acid vector in the form of specific insertion; Preferably, the sequence of the TTA1 aptamer is: SEQ ID NO:265: CCTGCACTTGGCTTGGATTTCAGAAGGGAGACCC; Drug 99): TTA1 aptamer-2*Survivin siRNA-DNA vector; The DNA vector is the 13th group of the nucleic acid vector according to claim 4, the TTA1 aptamer is connected to the 5' end of the b sequence through a transition sequence, the two positive strands of the survivin siRNA are connected to the 3' ends of the b sequence and the c sequence, and the two antisense strands of the survivin siRNA are connected to the 3' ends of the b sequence and the c chain through complementary pairing with the positive strands of the survivin siRNA; Preferably, the TTA1 aptamer is: SEQ ID NO: 265: CCTGCACTTGGCTTGGATTTCAGAAGGGAGACCC; Preferably, the antisense strand of the Survivin siRNA is: SEQ ID NO: 300: UGUGACAGAUAAGGAACCUGCAG; The sense strand of the Survivin siRNA is: SEQ ID NO: 100: GCAGGUUCCUUAUCUGUCACAUU; both the sense strand and the antisense strand of the Survivin siRNA have thiolation modifications in the phosphate backbone between the first 3 adjacent nucleotides at the 5' end and between the last 3 adjacent nucleotides at the 3' end; Drug 100): CD16a aptamer-CD40 aptamer-CpG2006-DNA vector, wherein the DNA vector is the group 6) of the nucleic acid vector according to claim 4, the CD16a aptamer is connected to the 5' end of the a sequence through a transition sequence, the CD40 aptamer is connected to the 3' end of the b sequence through the transition sequence, and the CpG2006 is connected to the 5' end of the c sequence through the transition sequence; Preferably, the sequence of the CD16a aptamer is SEQ ID NO: 157: CCACTGCGGGGGTCTATACGTGAGGAAGAAGTGG, the 1st to 3rd phosphate backbones at the 5' end are thio-modified; Preferably, the sequence of the CD40 aptamer is SEQ ID NO: 154: CCAACGAGTAGGCGATAGCGCGTGG, the 1st to 3rd phosphate backbones at the 5' end are thio-modified; Preferably, the sequence of CpG2006 is SEQ ID NO: 57: TCGTCGTTTTGTCGTTTTGTCGTT, and the phosphate backbones between adjacent nucleotides are all thio-modified; Preferably, the transition sequence is TTTTT.

13. A pharmaceutical composition, characterized in that The invention comprises any one or more of the nucleic acid drugs according to any one of claims 6 to 12, and optionally a pharmaceutically acceptable carrier and / or excipient.

14. The composition according to claim 13, characterized in that At least one drug in the pharmaceutical composition is selected from the nucleic acid drug according to claim 12, and the pharmaceutical composition is selected from any one of the following combinations; Combination 1): the drug 2) + the drug 21); Combination 2): the drug 6) + the drug 26); Combination 3): the drug 6) + OX40 aptamer in RNA form; Combination 4): the drug 3) + the drug 26); Combination 5): the drug 3) + the drug 21) + OX40 aptamer in DNA form; Combination 6): the drug 4) + the drug 21) + the OX40 aptamer in DNA form; Combination 7): the drug 4) + the drug 21); Combination 8): the drug 3) + the drug 23); Combination 9): the drug 4) + the drug 23); Combination 10): the drug 3) + the drug 24) + the OX40 aptamer in DNA form; Combination 11): the drug 3) + the drug 41); Combination 12): the drug 5) + the drug 41); Combination 13): the drug 5) + the drug 96); _ Combination 14): drug 96) + the drug 41); Combination 15): the drug 3) + the drug 97) + the OX40 aptamer in DNA form; Combination 16): the drug 4) + the drug 20) + the OX40 aptamer in DNA form; Combination 17): the drug 4) + the drug 20); Combination 18): the drug 7) + the drug 25) + the OX40 aptamer in DNA form; Combination 19): the drug 1) + the drug 18) + the drug 98); Combination 20): the drug 1) + the drug 18) + the OX40 aptamer in DNA form + the drug 99); Combination 21): the drug 3) + the drug 18) + the OX40 aptamer in DNA form; Combination 22): the drug 3) + the drug 18); Combination 23): the drug 3) + the OX40 aptamer in DNA form; Combination 24): the drug 3) + the drug 18) + an OX40 aptamer in the form of a locked nucleic acid; Combination 25): the drug 3) + the drug 18) + the OX40 aptamer in RNA form; Combination 26): the drug 3) + the drug 18) + the CD40 aptamer in DNA form Combination 27): the drug 3) + the drug 20) + the CD40 aptamer in DNA form; Combination 28): the drug 4) + the drug 19) + the CD40 aptamer in DNA form; Wherein, the sequence of the OX40 aptamer in DNA form is: SEQ ID NO:227:CAGTCTGCATCGTAGGATTAGCCACCGUATCTTTCCCAC; The sequence of the OX40 aptamer in RNA form is: SEQ ID NO:226: GGGAGGACGAUGCGGCAGUCUGCAUCGUAGGAAUCGCCACCGUAUACUUUC CCACCAGACGACUCGCUGAGGAUCCGAGA; The locked nucleic acid-form OX40 aptamer is a DNA-form OX40 aptamer in which the first 5 nucleotides at the 5' end and the first 4 nucleotides at the 3' end have locked nucleic acid modifications.

15. Use of the nucleic acid vector according to any one of claims 1 to 5, the nucleic acid drug according to any one of claims 6 to 12, or the pharmaceutical composition according to claim 13 or 14 in the preparation of a medicament for treating a tumor, a liver disease other than liver cancer, or a disease caused by coronavirus infection.

16. The use according to claim 15, characterized in that The liver disease other than liver cancer is hepatitis B or hepatitis C; the disease caused by coronavirus infection includes COVID-19; the tumor is andrological tumor, gynecological tumor, respiratory system tumor, digestive system tumor, hematological tumor, urinary system tumor, bone marrow tumor, neurological tumor, dermatological tumor, general surgical tumor or ENT tumor; Preferably, the male tumor is prostate cancer, penile cancer, testicular tumor or male urethral cancer, the gynecological tumor is ovarian cancer, cervical cancer, mesothelioma, uterine fibroids, vulvar cancer or malignant hydatidiform mole, the respiratory system tumor is lung cancer, non-small cell lung cancer, small cell lung cancer, nasopharyngeal carcinoma, tracheal tumor, lung cancer metastasis, inflammatory pseudotumor or radiation lung cancer, the digestive system tumor is liver cancer, gastric cancer, colorectal cancer, gallbladder cancer, esophageal cancer, rectal cancer, pancreatic cancer or colon cancer, and the hematological tumor is leukemia. , lymphoma, lymphosarcoma or multiple myeloma, the renal cancer, bladder cancer or urinary cancer, the bone marrow tumor is giant cell tumor of bone, osteochondroma or osteosarcoma, the neurological tumor is brain tumor, meningioma, brain tuberculoma, pituitary tumor, neuroblastoma, glioblastoma or brain glioma, the dermatological tumor is skin cancer or melanoma, the general surgical tumor is breast cancer, lipoma, thyroid cancer or thyroid tumor, the ENT tumor is oral cancer, tongue cancer, laryngeal cancer, middle ear cancer, gingival cancer or orbital tumor; Preferably, the drug is administered by tumor administration, intravenous administration or intraperitoneal administration during the application process; Preferably, the daily dosage of the drug during the application process is 0.1 μg / Kg to 100 mg / Kg.

17. A method for preparing a nucleic acid drug according to any one of claims 6 to 16, characterized in that: The preparation method comprises obtaining the nucleic acid drug by self-assembling at least one chain of a nucleic acid vector containing sequence a, sequence b and sequence c and at least one oligonucleotide effector molecule mounted on the nucleic acid vector; Wherein, the oligonucleotide effector molecule is selected from at least one of the following: nucleic acid immunostimulant, nucleic acid aptamer, siRNA, miRNA and ASO.

18. The preparation method according to claim 17, characterized in that: The nucleic acid drug is obtained by self-assembly of 2 to 8, preferably 3 to 6 chains.

19. The preparation method according to claim 18, characterized in that: When more than 3 chains are self-assembled, the preparation method comprises: Providing the following three modified or unmodified sequences for self-assembly to form a nucleic acid vector: sequence a, sequence b and sequence c, wherein the modification refers to modification with a chemical small molecule having a targeting effect; By means of sequence complementarity, at least one sequence of the oligonucleotide effector molecule is mounted on the 5' end and / or 3' end of at least one of the a sequence, the b sequence and the c sequence of the nucleic acid vector; Wherein, the oligonucleotide effector molecule is selected from at least one of the following: nucleic acid immunostimulant, nucleic acid aptamer, siRNA, miRNA and ASO.

20. The preparation method according to claim 19, characterized in that: When the oligonucleotide effector molecule comprises siRNA, The sense strand of the siRNA is synthesized at the 5' end and / or 3' end of at least one of the modified or unmodified a sequence, the b sequence and the c sequence, and the antisense strand of the siRNA is self-assembled with the modified or unmodified a sequence, the b sequence and the c sequence, so that the siRNA is connected to the nucleic acid vector through complementary pairing of the antisense strand of the siRNA and the sense strand of the siRNA; Preferably, the sense strand of the siRNA is directly synthesized at the 5' end and / or 3' end of at least one of the a sequence, the b sequence and the c sequence through a transition sequence; Preferably, the transition sequence is selected from 2 to 8, preferably 3 to 6 consecutive T, A or U.

21. The preparation method according to claim 19, characterized in that: The oligonucleotide effector molecule includes miRNA and / or the nucleic acid immunostimulator, the miRNA is directly synthesized and / or the nucleic acid immunostimulator is synthesized through a transition sequence at the 5' end and / or 3' end of at least one of the modified or unmodified a sequence, the b sequence and the c sequence, and the miRNA and / or the nucleic acid immunostimulator is mounted on the nucleic acid carrier through self-assembly of the modified or unmodified a sequence, the b sequence and the c sequence; Preferably, the transition sequence is selected from 2 to 8, preferably 3 to 6 consecutive T or A.

22. The preparation method according to claim 19, characterized in that: The oligonucleotide effector molecule includes a nucleic acid aptamer, which is synthesized at the 5' end and / or 3' end of at least one of the modified or unmodified a sequence, the b sequence and the c sequence, and the nucleic acid aptamer is mounted on the nucleic acid vector through self-assembly of the modified or unmodified a sequence, the b sequence and the c sequence; Preferably, the nucleic acid aptamer is directly synthesized at the 5' end and / or 3' end of at least one of the a sequence, the b sequence and the c sequence through a transition sequence; Preferably, the transition sequence is selected from 2 to 8, preferably 3 to 6 consecutive T or A.

23. The preparation method according to claim 20, characterized in that: When the oligonucleotide effector molecule further comprises the nucleic acid immunostimulator and / or the nucleic acid aptamer, The nucleic acid immunostimulator is synthesized through a transition sequence at the 5' end and / or 3' end of at least one of the modified or unmodified a sequence, the b sequence and the c sequence, and is different from one end of the siRNA sense strand, and / or synthesizing the nucleic acid aptamer at the 5' end of the antisense strand of the siRNA through the transition sequence to obtain an aptamer-siRNA fragment; The aptamer-siRNA fragment is co-incubated with the modified or unmodified a sequence, the b sequence and the c sequence that synthesize the nucleic acid immunostimulant to perform the self-assembly, so that the nucleic acid aptamer is mounted on the nucleic acid carrier through the complementarity of the antisense strand of the siRNA and the sense strand of the siRNA.

24. The preparation method according to claim 22, characterized in that: When the oligonucleotide effector molecule further comprises the miRNA and the nucleic acid aptamer, The nucleic acid aptamer is synthesized at the 5' end or 3' end of the miRNA to obtain a nucleic acid aptamer-miRNA fusion single-stranded sequence; The nucleic acid aptamer-miRNA fusion single-stranded sequence is made to participate in the self-assembly, so that the nucleic acid aptamer and the miRNA are mounted on the nucleic acid carrier.

25. The preparation method according to claim 22, characterized in that: When the oligonucleotide effector molecule further comprises the nucleic acid immunostimulator and the nucleic acid aptamer, The nucleic acid immunostimulator and the nucleic acid aptamer are independently synthesized at any end of at least one of the modified or unmodified a sequence, the b sequence and the c sequence to obtain the nucleic acid immunostimulator and / or the nucleic acid aptamer fusion sequence, The nucleic acid immunostimulator and / or the nucleic acid aptamer fusion sequence are made to participate in the self-assembly, so that the nucleic acid aptamer and the nucleic acid immunostimulator are mounted on the nucleic acid carrier.

26. The preparation method according to claim 19, characterized in that: The a sequence, the b sequence and the c sequence respectively include the carrier backbone sequence and the single-stranded bonding bridge sequence, and one or more oligonucleotide effector molecules self-assemble with the a sequence, the b sequence and the c sequence through the complementary sequence of the single-stranded bonding bridge sequence to form the nucleic acid drug; Preferably, the a sequence, the b sequence and the c sequence are respectively as follows: The a sequence is: SEQ ID NO: 15: GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC, where the underlined part is the single-stranded connecting bridge sequence A; The b sequence is: SEQ ID NO: 16: CCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, where the underlined part is a single strand Connecting bridge sequence B; The c sequence is: SEQ ID NO: 17: GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG, where the underlined part is Single-stranded connecting bridge sequence C.

27. The preparation method according to claim 25, characterized in that: The nucleic acid drug is a CpG2006-CD40 aptamer-PD-L1 aptamer-DNA vector, and the preparation method includes any one of the following self-assembly methods; 1) Three chains self-assemble, where the three chains are: CpG2006-a sequence: SEQ ID NO:309: TCGTCGTTTTGTCGTTTTGTCGTTTTTTTGCGACGCCCACGAGCGTTCCGGGAG AGGAGC, the phosphate backbone between the adjacent nucleotides at positions 1-24 before the 5' end has a thiolation modification, TTTTT is a transition sequence, the sequence before TTTTT is the CpG2006 sequence, and the sequence after TTTTT is the a sequence; CD40 aptamer-b sequence: SEQ ID NO: 330: CCAACGAGTAGGCGATAGCGCGTGGTTTTTGCTCCTCTCCCGGTTCGCCGCGAGCCGCG, the phosphate backbone between the adjacent nucleotides at positions 1 to 5 before the 5' end has a thio modification, TTTTT is a transition sequence, the sequence before TTTTT is the CD40 aptamer sequence, and the sequence after TTTTT is the b sequence; and PD-L1 aptamer-c sequence: SEQ ID NO: 331: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGTTTTTTCCGG GCTCGCGGCCATAGCCGTGGGCGTCGC, the phosphate backbone between the adjacent nucleotides at the 1-5 positions before the 5' end has a thio modification, TTTTT is a transition sequence, the sequence before TTTTT is the sequence of the PD-L1 aptamer, and the sequence after TTTTT is the c sequence; 2) 4 chains self-assemble, where the 4 chains are: CpG2006-a sequence: SEQ ID NO:309: TCGTCGTTTTGTCGTTTTGTCGTTTTTTTGCGACGCCCACGAGCGTTCCGGGAG AGGAGC, the phosphate backbone between the adjacent nucleotides at positions 1-24 before the 5' end has a thiolation modification, TTTTT is a transition sequence, the sequence before TTTTT is the CpG2006 sequence, and the sequence after TTTTT is the a sequence; CD40 aptamer-b sequence: SEQ ID NO: 339: CCAACGAGTAGGCGATAGCGCGTGGTTTGCTCCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, the phosphate backbone between the adjacent nucleotides at the 1st to 4th positions before the 5' end has a thio modification, TTT is a transition sequence, the sequence before TTT is the CD40 aptamer sequence, and the sequence after TTT is the b sequence; A complementary sequence B' of PD-L1 aptamer-transition sequence-single-stranded bridge sequence B: SEQ ID NO: 336: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGTTTTTTCACGGCCGCGCCGA, with a thio modification on the phosphate backbone between the adjacent nucleotides at positions 1-4 before the 5' end, TTTTT is a transition sequence, the sequence before TTTTT is the PD-L1 aptamer sequence, and the sequence after TTTTT is the complementary sequence B'; and c-sequence: SEQ ID NO: 340: GGCTCGCGGCCATAGCCGTGGGCGTCGC; or The 4 chains are: CpG2006--transition sequence-complementary sequence C' of single-stranded connecting bridge sequence C: SEQ ID NO: 341: TCGTCGTTTTGTCGTTTTGTCGTTTTTTTTCAGCAGCAGCAGCA, the phosphate backbone between the adjacent nucleotides 1-24 before the 5' end has a thio modification, TTTTT is the transition sequence, the sequence before TTTTT is the CpG2006 sequence, and the sequence after TTTTT is the complementary sequence C'; a Sequence: SEQ ID NO: 18: GCGACGCCCACGAGCGTTCCGGGAGAGGAGC; CD40 aptamer-b sequence: SEQ ID NO: 339: CCAACGAGTAGGCGATAGCGCGTGGTTTGCTCCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, the phosphate backbone between the adjacent nucleotides at positions 1-4 before the 5' end has a thio modification, TTT is a transition sequence, the sequence before TTT is the CD40 aptamer sequence, and the sequence after TTT is the b sequence; PD-L1 aptamer-c sequence: SEQ ID NO: 342: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGTTTTTTGGCTCGCGGCCATAGCCGTGGGCGTCGC, the phosphate backbone between the adjacent nucleotides at positions 1-4 before the 5' end has a thio modification, TTTTT is a transition sequence, the sequence before TTTTT is the PD-L1 aptamer sequence, and the sequence after TTTTT is the c sequence; 3) 5 chains self-assemble, where the 5 chains are: aSequence: SEQ ID NO:15: GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC; CD40 aptamer-transition sequence-b sequence: SEQ ID NO: 339: CCAACGAGTAGGCGATAGCGCGTGGTTTGCTCCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG, the phosphate backbone between the adjacent nucleotides at positions 1 to 4 before the 5' end has a thio modification, TTT is the transition sequence, the sequence before TTT is the CD40 aptamer sequence, and the sequence after TTT is the b sequence; PD-L1 aptamer-transition sequence-single-stranded bridge sequence B complementary sequence B': SEQ ID NO: 336: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGTTTTTTCACGGCC GCGCCGA, the phosphate backbone between the adjacent nucleotides at the 1-4 positions before the 5' end has a thio modification, TTTTT is a transition sequence, the sequence before TTTTT is the sequence of the PD-L1 aptamer, and the sequence after TTTTT is the complementary sequence B'; The complementary sequence C' of CpG2006 sequence-transition sequence-single-stranded bridge sequence C: SEQ ID NO: 337: TCGTCGTTTTGTCGTTTTGTCGTTTTTTTCAGCAGCAGCAGCA, the phosphate backbone between the adjacent nucleotides 1-24 before the 5' end has a thio modification, TTTTT is the transition sequence, the sequence before TTTTT is the CpG2006 sequence, and the sequence after TTTTT is the complementary sequence C'; c sequence: SEQ ID NO: 17: GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG; Or the 5 chains are: CpG2006-transition sequence-a sequence: SEQ ID NO: 343: TCGTCGTTTTGTCGTTTTGTCGTTTTTTTGACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC, the phosphate backbone between the adjacent nucleotides 1-24 before the 5' end has a thio modification, TTTTT is the transition sequence, the sequence before TTTTT is the CpG2006 sequence, and the sequence after TTTTT is the a sequence; The complementary sequence A' of CD40 aptamer-transition sequence-single-stranded bridge sequence A: SEQ ID NO: 338: GCCAACGAGTAGGCGATAGCGCGTGGCTTTTTGCCACCGTGCTACA, the phosphate backbone between the adjacent nucleotides at positions 1-4 before the 5' end has a thio modification, TTTTT is the transition sequence, the sequence before TTTTT is the sequence of the CD40 aptamer, and the sequence after TTTTT is the complementary sequence A'; b sequence: SEQ ID NO: 16: CCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG; The complementary sequence B' of PD-L1 aptamer-transition sequence-single-stranded bridge sequence B: SEQ ID NO: 336: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGTTTTTTCACGGCCGCGCCGA, the phosphate backbone between the adjacent nucleotides at positions 1-4 before the 5' end has a thio modification, TTTTT is the transition sequence, the sequence before TTTTT is the PD-L1 aptamer sequence, and the sequence after TTTTT is the complementary sequence B'; c sequence: SEQ ID NO: 340: GGCTCGCGGCCATAGCCGTGGGCGTCGC; 4) 6 chains self-assemble, where the 6 chains are: aSequence: SEQ ID NO:15: GACGCCCACGAGCGTTCCGGGAGAGGTGTAGCACGGTGGC; b sequence: SEQ ID NO: 16: CCTCTCCCGGTTCGCCGCGAGCCTCGGCGCGGCCGTG; c sequence: SEQ ID NO: 17: GGCTCGCGGCCATAGCCGTGGGCGTCTGCTGCTGCTGCTG; CpG2006-transition sequence-single-stranded bridge sequence C complementary sequence C': SEQ ID NO: 337: TCGTCGTTTTGTCGTTTTGTCGTTTTTTTCAGCAGCAGCAGCA; 5' end front 1-24 phase There is a thio modification on the phosphate backbone between adjacent nucleotides, TTTTT is the transition sequence, the sequence before TTTTT is the CpG2006 sequence, and the sequence after TTTTT is the complementary sequence C'; The complementary sequence A' of CD40 aptamer-transition sequence-single-stranded bridge sequence A: SEQ ID NO: 338: GCCAACGAGTAGGCGATAGCGCGTGGCTTTTTGCCACCGTGCTACA, the phosphate backbone between the adjacent nucleotides at positions 1-4 before the 5' end has a thio modification, TTTTT is the transition sequence, the sequence before TTTTT is the sequence of the CD40 aptamer, and the sequence after TTTTT is the complementary sequence A'; The complementary sequence B' of PD-L1 aptamer-transition sequence-single-stranded connecting bridge sequence B: SEQ ID NO: 336: ACGGGCCACATCAACTCATTGATAGACAATGCGTCCACTGCCCGTTTTTTCACGGCCGCGCCGA, the phosphate backbone between the adjacent nucleotides at positions 1-4 before the 5' end has a thio modification, TTTTT is the transition sequence, the sequence before TTTTT is the PD-L1 aptamer, and the sequence after TTTTT is the complementary sequence B'.

28. The preparation method according to any one of claims 17 to 27, characterized in that: The self-assembly step comprises: Dissolving the modified or unmodified a sequence, b sequence, c sequence and the optional separately synthesized sequence of the oligonucleotide effector molecule carrying at least one of the oligonucleotide effector molecules in an assembly solution and sequentially performing denaturation reaction and renaturation reaction to form a self-assembly crude product; Purifying, eluting and drying the crude self-assembly product in sequence to obtain a targeting nucleic acid vector carrying at least one oligonucleotide effector molecule; Preferably, the molar ratio of the a sequence, the b sequence and the c sequence is 0.90-1.10:0.90-1.10:0.90-1.10, more preferably 1:1:1; Preferably, the assembly liquid is TMS aqueous solution, sodium chloride aqueous solution, magnesium chloride aqueous solution or purified water; Preferably, the temperature of the denaturation reaction is 80 to 99°C, more preferably 85 to 99°C, and further preselected to be 90 to 99°C; Preferably, after the denaturation reaction is completed, the reaction system is cooled to the renaturation temperature to perform the renaturation reaction, and finally cooled to obtain the self-assembled crude product; wherein the insulation temperature is 70-50°C, more preferably 65-55°C, and further preferably 63-57°C; the renaturation reaction time is 3-15 min, more preferably 3-10 min, and further preferably 3-5 min; Preferably, in the process of cooling the reaction system to the insulation temperature, the cooling rate is 2 to 10°C / min, more preferably 2 to 6°C / min, and further preferably 2 to 3°C / min; Preferably, the cooling end point temperature is 0 to 25°C, more preferably 0 to 15°C, and further preferably 0 to 4°C; Preferably, the pH value of the denaturation reaction is 5.4-8.8.

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