Oligonucleotide, oligonucleotide conjugate, composition, and use

Abstract

Provided is a single-stranded oligonucleotide having a length of 16-30 nucleotides. The single-stranded oligonucleotide and CFB mRNA have sufficient complementarity to mediate an RNAi effect. Each nucleotide in the single-stranded oligonucleotide is a modified or unmodified nucleotide. At least one nucleotide in the single-stranded oligonucleotide is a nucleotide X, and at least one nucleotide is a fluoro-modified nucleotide. In the direction from the 5' end to the 3' end, at least one nucleotide X is located after the eighth nucleotide of the single-stranded oligonucleotide and spaced apart from the eighth nucleotide of the single-stranded oligonucleotide by 4-7 nucleotides. Each nucleotide X is a deoxynucleotide or an unmodified nucleotide. Further provided are a double-stranded oligonucleotide comprising the single-stranded oligonucleotide as an antisense strand, an oligonucleotide conjugate, and a pharmaceutical composition.

Description

Oligonucleotides, oligonucleotide conjugates, and compositions and uses TECHNICAL FIELD The present disclosure relates to a single-stranded oligonucleotide, and also relates to a double-stranded oligonucleotide comprising the single-stranded oligonucleotide as an antisense strand, an oligonucleotide conjugate, a composition, uses thereof and a preparation method. The present disclosure provides a double-stranded oligonucleotide for inhibiting the expression of complement factor B (CFB) gene and applications in treating, preventing or ameliorating complement system related diseases. BACKGROUND The complement system is composed of three parts, the classical pathway, the lectin pathway and the alternative pathway, which all converge at the formation of the complement component 3 (C3) convertase complex. These enzyme complexes are capable of cleaving the complement component C3 protein into C3a and C3b. Once C3 is cleaved, C3b becomes part of a complex that then cleaves C5 into C5a and C5b. Cleaved C5b is one of the key components of the membrane attack complex, the main complement pathway effector. Therefore, C3 is considered a core component in the activation pathway of the complement system. Complement factor B (CFB) plays an important role in the activation of the alternative pathway. When CFB binds to C3b (e.g. on the cell surface), it is more easily cleaved by factor D, forming the catalytically active C3 convertase (C3bBb), which in turn initiates the amplification loop of C3 activation, amplifying the activation effect of the complement system. Complement factor B (CFB) is mainly synthesized in the liver and stored in the plasma at high concentrations. In addition, CFB is also synthesized at lower levels in several extrahepatic sites. Inappropriate activation of the complement system can trigger a series of serious diseases, including C3 glomerulopathy, systemic lupus erythematosus (SLE, such as lupus nephritis), IgA nephropathy, diabetic nephropathy, polycystic kidney disease, membranous nephropathy, age-related macular degeneration, atypical hemolytic uremic syndrome, thrombotic microangiopathy, myasthenia gravis (MG), ischemia-reperfusion injury, paroxysmal nocturnal hemoglobinuria (PNH), and rheumatoid arthritis, etc. Given the significant threat these diseases pose to patient health, there is an urgent need in the art to develop and apply therapeutic solutions that can effectively regulate the imbalance of the complement system, with the aim of improving patient quality of life and curbing disease progression. In siRNA drugs, the antisense strand is the most important part that determines the performance of double-stranded oligonucleotides, which can specifically pair with the messenger RNA (mRNA) of the target gene, leading to the degradation or inactivation of mRNA, thereby inhibiting or blocking the expression of the gene. Given this unique mechanism, siRNA drugs show great potential and are expected to become an effective means of precisely regulating the imbalance of the complement system and treating complement-related diseases. SUMMARY The present application provides a single-stranded oligonucleotide, a double-stranded oligonucleotide comprising the single-stranded oligonucleotide of the present disclosure as an antisense strand, and an oligonucleotide conjugate, all of which exhibit good pharmaceutical activity and stability when targeting CFB mRNA. In one aspect, the present application provides a single-stranded oligonucleotide, the length of which is 16-30 nucleotides, which has sufficient complementarity with CFB mRNA to mediate an RNAi effect; each nucleotide in the single-stranded oligonucleotide is a modified or unmodified nucleotide, wherein at least one nucleotide in the single-stranded oligonucleotide is a nucleotide X, and at least one nucleotide is a fluorine-modified nucleotide; and, in the direction from the 5' end to the 3' end, at least one nucleotide X is located after the 8th nucleotide of the single-stranded oligonucleotide, and is spaced apart from the 8th nucleotide by 4-7 nucleotides; And, in the direction from the 5' end to the 3' end, if the 14th nucleotide of the single-stranded oligonucleotide is a nucleotide X, and all nucleotides from the 15th nucleotide and thereafter of the single-stranded oligonucleotide are modified nucleotides, then the 13th nucleotide of the single-stranded oligonucleotide is selected from one of an alkoxy-modified nucleotide, an alkyl-modified nucleotide, a substituted alkyl-modified nucleotide, an amine-modified nucleotide, a thermally unstable nucleotide, and a BNA; Each nucleotide X is a deoxynucleotide or an unmodified nucleotide. In another aspect, the present disclosure provides a double-stranded oligonucleotide, which contains a sense strand and an antisense strand, each nucleotide in the sense strand being a modified or unmodified nucleotide, the sense strand and the antisense strand being at least partially reverse complementary to form a double-stranded region, wherein the antisense strand is the single-stranded oligonucleotide of the present disclosure. In yet another aspect, the present disclosure also provides an oligonucleotide conjugate, which contains an oligonucleotide group and a delivery group conjugated to the oligonucleotide group, the oligonucleotide group being independently a group formed by removing one or more atoms or atom groups from the single-stranded oligonucleotide or the double-stranded oligonucleotide of the present disclosure. In yet another aspect, the present disclosure also provides a pharmaceutically acceptable salt of the single-stranded oligonucleotide, the double-stranded oligonucleotide, or the oligonucleotide conjugate of the present disclosure. In yet another aspect, the present disclosure also provides a pharmaceutical composition, which contains one or more of the single-stranded oligonucleotide, the double-stranded oligonucleotide, the oligonucleotide conjugate, and the pharmaceutically acceptable salt of the present disclosure, and a pharmaceutically acceptable excipient. In yet another aspect, the present disclosure also provides a use of one or more of the single-stranded oligonucleotides, double-stranded oligonucleotides, oligonucleotide conjugates, pharmaceutically acceptable salts, and pharmaceutical compositions of the present disclosure in the manufacture of a medicament for the treatment and / or prevention of a disease or a symptom associated with CFB mRNA level. In yet another aspect, the present disclosure also provides a method of treating and / or preventing a disease or a symptom associated with CFB mRNA level, the method comprising administering to a subject in need thereof an effective amount of one or more of the single-stranded oligonucleotides, double-stranded oligonucleotides, oligonucleotide conjugates, pharmaceutically acceptable salts, and pharmaceutical compositions of the present disclosure. In yet another aspect, the present disclosure also provides a method of modulating the expression level of CFB mRNA in a cell, the method comprising contacting the cell with an effective amount of one or more of the single-stranded oligonucleotides, double-stranded oligonucleotides, oligonucleotide conjugates, pharmaceutically acceptable salts, and pharmaceutical compositions of the present disclosure. In yet another aspect, the present disclosure also provides one or more of the single-stranded oligonucleotides, double-stranded oligonucleotides, oligonucleotide conjugates, pharmaceutically acceptable salts, and pharmaceutical compositions of the present disclosure for use as a medicament. In yet another aspect, the present disclosure also provides a cell expressing CFB mRNA, the cell comprising one or more of the single-stranded oligonucleotides, double-stranded oligonucleotides, oligonucleotide conjugates, pharmaceutically acceptable salts, and pharmaceutical compositions of the present disclosure. In addition, the present disclosure also provides a kit comprising one or more of the single-stranded oligonucleotides, double-stranded oligonucleotides, oligonucleotide conjugates, pharmaceutically acceptable salts, and pharmaceutical compositions of the present disclosure. Incorporated by reference All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually incorporated by reference. Advantages One or more of the double-stranded oligonucleotides, oligonucleotide conjugates, and pharmaceutical compositions comprising the single-stranded oligonucleotides described in the present disclosure as the antisense strand have higher activity in modulating CFB mRNA, and have higher long-acting property. For example, the double-stranded oligonucleotides (e.g., siRNA), oligonucleotide conjugates and / or pharmaceutical compositions containing the single-stranded oligonucleotide of the present disclosure as the antisense strand show excellent mRNA inhibition effect on CFB gene expression. For example, compared with the blank control group, the siRNA conjugates all exhibit excellent inhibition effect at a concentration of 50 nM in the in vitro hCFB transgenic mouse liver primary cells, and the CFB mRNA inhibition rate is more than 87%; further, among the 25 different conjugates, as many as 14 achieve more than 95% CFB mRNA inhibition rate at the same concentration. For another example, the siRNA conjugates all exhibit excellent inhibition effect at a concentration of 5 nM in the in vitro hCFB transgenic mouse liver primary cells, and the CFB mRNA inhibition rate is more than 86%; and most of the conjugates have more than 90% CFB mRNA inhibition rate. Meanwhile, at a low concentration of 0.5 nM, the conjugates of the present disclosure have a highest inhibition rate of 86.5%, also showing a good effect on inhibiting CFB mRNA expression. For another example, in the hCFB transgenic mouse liver primary cells, the siRNA conjugates of the present disclosure have an inhibition rate of 96.6%-97.9% at a concentration of 5 nM, and still maintain a high inhibition rate of 95.3%-97.1% at a low concentration of 0.5 nM, indicating that the conjugates provided by the present disclosure have high and stable CFB mRNA inhibition activity. For another example, in the in vitro HepG2 cell experiment, the siRNA conjugates provided by the present disclosure have an inhibition rate of more than 79% on CFB mRNA at a concentration of 50 nM, and even can reach 85.4%. At a concentration of 0.5 nM, all the conjugates have an inhibition rate of more than 68.3% on CFB mRNA, and even can reach 78.3%. It indicates that the conjugates provided by the present disclosure have excellent inhibition activity on CFB mRNA. For another example, in the in vitro monkey primary cells, the siRNA conjugates provided by the present disclosure all have an inhibition rate of more than 90% at a low concentration of 0.5 nM, and have excellent in vitro inhibition activity. On the other hand, the siRNA of the present disclosure containing the antisense strand, the conjugates of the present disclosure and / or the pharmaceutical compositions have long-acting mRNA inhibition effect and protein expression inhibition effect on CFB gene expression. For example, in the hCFB transgenic mice administered with the conjugates at the same concentration (3 mg / kg) for 36 days, all the conjugates can continuously inhibit the expression of hCFB protein during the experiment, and at the 8th day, the conjugates provided by the present disclosure have an inhibition rate of more than 68% on hCFB protein in the hCFB transgenic mice, and even can reach 88.8%; at the 22nd day, the conjugates provided by the present disclosure still have an inhibition rate of 85.7% on hCFB protein in the hCFB transgenic mice; at the 50th day, the conjugates provided by the present disclosure still have a higher inhibition rate of 54.9% on hCFB protein in the hCFB transgenic mice.For example, in the hCFB transgenic mice administered with 3 mg / kg of the conjugate, the inhibition rates of the hCFB protein of all the tested conjugates were all over 80% on day 8 and day 15 after administration, and the inhibitory effect lasted until the end of the experiment (D57). Even the conjugates provided by the present disclosure maintained the inhibition rate of the hCFB protein in the hCFB transgenic mice at over 75% during the 57-day experiment period, and the highest inhibition rate reached 91%. For example, in the hCFB transgenic mice administered with 3 mg / kg of the conjugate, the inhibition rates of the hCFB protein in the hCFB transgenic mice of the conjugates provided by the present disclosure were all significantly higher than those of the reference conjugates on day 43. For example, in the hCFB transgenic mice administered with 1 mg / kg of the conjugate, the inhibition rates of the hCFB protein in the hCFB transgenic mice of the conjugates provided by the present disclosure were all significantly higher than those of the reference conjugates during the 43-day experiment period, especially on day 43, while the reference conjugate had no inhibitory activity on the hCFB protein in the hCFB transgenic mice, the inhibition rate of the hCFB protein in the hCFB transgenic mice of the conjugates provided by the present disclosure on day 43 was still 39.1%. The above indicates that the conjugates provided by the present disclosure can stably inhibit the hCFB protein and have long-acting effect. Therefore, the conjugates of the present disclosure can stably and efficiently inhibit the expression of CFB mRNA for a long time. The conjugates of the present disclosure have good CFB mRNA regulating activity, show significant long-acting pharmaceutical activity in the preparation of drugs for the treatment and / or prevention of diseases or symptoms related to the expression of CFB mRNA, and have excellent development prospects. DETAILED DESCRIPTION The detailed description of the present disclosure is described in detail below. It should be understood that the detailed description described herein is only used to illustrate and explain the present disclosure, and is not used to limit the present disclosure. In the present disclosure, the CFB mRNA refers to the CFB mRNA expressed in mammalian cells. In the present disclosure, the CFB mRNA refers to the mRNA of the sequence shown in Genbank registration number NM_001710.6. Further, unless otherwise specified, the term “CFB gene” used in the present disclosure refers to the gene transcribing the above-mentioned CFB mRNA. DEFINITIONS In the context of this document, the expressions "complementary" or "reverse complementary" are used interchangeably and have the meaning well known to those skilled in the art, i.e. in a double-stranded nucleic acid structure, the bases of one strand each form a hydrogen bond between base pairs in a complementary manner with the bases on the other strand, effecting base pairing, forming Watson-Crick base pairs. A "base pair" refers to two bases that form a base pair. In DNA, the purine base adenine (A) always pairs with the pyrimidine base thymine (T) (or in RNA with uracil (U)); the purine base guanine (G) always pairs with the pyrimidine base cytosine (C). Each base pair comprises one purine and one pyrimidine. When adenine on one strand always pairs with thymine (or uracil) on the other strand, and guanine always pairs with cytosine, the two strands are considered to be complementary to each other, and the sequence of one strand can be inferred from the sequence of its complementary strand. When the bases are modified, as long as the above-mentioned purine-pyrimidine pairing relationship is not affected (including but not limited to the number and strength of hydrogen bonds between bases), the modified bases are also considered to be able to form complementary pairing. Accordingly, "mismatch" or "base mismatch" in the art means that the bases at the corresponding positions between the two single-stranded nucleic acids involved do not pair in a complementary manner; when the corresponding position includes an abasic nucleotide, it is also considered to form a mismatch with the base on the other strand. In the above and below, "nucleotide sequence A is substantially reverse complementary, substantially reverse complementary or completely reverse complementary to nucleotide sequence B over a span of X nucleotides" means that there is a continuous nucleotide sequence A' of length X in nucleotide sequence A which is substantially reverse complementary, substantially reverse complementary or completely reverse complementary to a continuous nucleotide sequence B' of the same length X in nucleotide sequence B. Unless specifically stated otherwise, in the context above and below, a reference to an oligonucleotide and / or oligonucleotide conjugate provided by the application or method of the present disclosure, including but not limited to an oligonucleotide and / or oligonucleotide conjugate represented by any of the structural formulae provided by the application or method of the present disclosure, also refers to a pharmaceutically acceptable salt of the conjugate, depending on the context. In the foregoing and hereinafter, particularly in describing the preparation of a single-stranded oligonucleotide, double-stranded oligonucleotide, pharmaceutical composition, or oligonucleotide conjugate of the disclosure, unless otherwise specified, the nucleoside monomer refers to modified or unmodified nucleoside phosphoramidite monomers (unmodified or modified RNA phosphoramidites, sometimes also referred to as Nucleoside phosphoramidites) used in the phosphoramidite solid phase synthesis according to the kind and order of nucleotides in the single-stranded oligonucleotide, double-stranded oligonucleotide, or oligonucleotide conjugate to be prepared. The phosphoramidite solid phase synthesis is a method commonly used in RNA synthesis known to those skilled in the art. All nucleoside monomers used in the disclosure are commercially available. Those skilled in the art will appreciate that, for any group containing one or more substituents, such groups are not intended to introduce any substituents or substituent patterns that are spatially impractical, synthetically non-feasible, and / or inherently unstable. As used herein, "alkyl" refers to saturated straight and / or branched chain hydrocarbon groups having the specified number of carbon atoms, typically from 1 to 20 carbon atoms, for example, from 1 to 10 carbon atoms, such as from 1 to 8 or from 1 to 6 carbon atoms. For example, C1-C6 alkyl includes straight and branched chain alkyl groups of from 1 to 6 carbon atoms. When reference is made to an alkyl residue having a particular number of carbons, it is intended to encompass all branched and straight chain forms having that number of carbons; thus, for example, "butyl" is meant to include n-butyl, sec-butyl, iso-butyl and t-butyl; "propyl" includes n-propyl and iso-propyl. Alkylene is a subset of alkyl, referring to the same residues as alkyl, but having two points of attachment. As used herein, "alkoxy" refers to an alkyl group of the specified number of carbon atoms attached via an oxygen bridge, for example, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, sec-butoxy, t-butoxy, pentoxy, 2-pentoxy, isopentoxy, neopentoxy, hexoxy, 2-hexoxy, 3-hexoxy, 3-methylpentoxy, and the like. Alkoxy groups typically have from 1 to 10, from 1 to 8, from 1 to 6, or from 1 to 4 carbon atoms attached via an oxygen bridge. As used herein, "alkoxy-modified alkyl" refers to a group formed upon substitution of one or more hydrogen atoms in an alkyl group with an alkoxy group, for example, methoxymethyl (CH3OCH2-), ethoxymethyl (CH3CH2OCH2-), methoxyethyl (CH3OCH2CH2-), and the like. As used herein, "alkenyl" refers to an unsaturated branched or straight-chain hydrocarbon group having at least one carbon-carbon double bond obtained by removing a hydrogen molecule from an adjacent carbon atom of a parent alkyl group. The group can be in either a cis or trans configuration of the double bond. Typical alkenyl groups include, but are not limited to: vinyl; propenyl, such as propyl-1-en-1-yl, propyl-1-en-2-yl, propyl-2-en-1-yl (allyl), propyl-2-en-2-yl; butenyl, such as buten-1-en-1-yl, buten-1-en-2-yl, 2-methylpropen-1-en-1-yl, buten-2-en-1-yl, buten-2-en-2-yl, buten-1,3-dien-1-yl, buten-1,3-dien-2-yl, etc. In some embodiments, the alkenyl group has 2 to 20 carbon atoms, while in other embodiments, it has 2 to 10, 2 to 8, or 2 to 6 carbon atoms. Subalkenyl groups are a subset of alkenyl groups, referring to residues that are identical to alkenyl groups but have two connection points. As used herein, "alkynyl" refers to an unsaturated branched or straight-chain hydrocarbon group having at least one carbon-carbon triple bond obtained by removing two hydrogen molecules from adjacent carbon atoms of a parent alkyl group. Typical alkynyl groups include, but are not limited to: ethynyl; propynyl, such as prop-1-yn-1-yl, prop-2-yn-1-yl; butynyl, such as but-1-yn-1-yl, but-1-yn-3-yl, but-3-yn-1-yl, etc. In some embodiments, the alkynyl group has 2 to 20 carbon atoms, while in other embodiments, it has 2 to 10, 2 to 8, or 2 to 6 carbon atoms. Ionynyl is a subset of alkynyl, referring to residues that are identical to alkynyl but have two connection sites. As used herein, "aryl" refers to a group derived from an aromatic monocyclic or polycyclic hydrocarbon ring system by removing a hydrogen atom from a ring carbon atom. This aromatic monocyclic or polycyclic hydrocarbon ring system contains only hydrogen and carbon atoms of 6 to 18, wherein at least one ring in the ring system is fully unsaturated, i.e., contains a cyclic, delocalized (4n+2)π-electron system according to Hückel's theory. Aryl groups include, but are not limited to, phenyl, fluorenyl, and naphthyl groups. Alearyl groups are a subset of aryl groups, referring to residues identical to aryl groups but with two connection points. As used herein, "heterocyclyl" refers to a radical derived from a monocyclic saturated or partially unsaturated, non-aromatic ring or bicyclic saturated or partially unsaturated heterocyclic hydrocarbon radical, wherein the bicyclic ring system is non-aromatic, the monocyclic or bicyclic ring has, for example, 3 to 10 members or 5 to 10 members, wherein at least 1 member and up to 5 members, particularly 1, 2, or 3 ring members are a heteroatom selected from N, O, and S, and the remaining ring atoms are carbon atoms, in stable combinations known to those skilled in the art. Among these, the heterocyclic nitrogen and sulfur atoms are optionally oxidized, and the nitrogen atoms are optionally quaternized. As used herein, the heterocycle can form a bicyclic ring with another ring system, i.e., one or two of the atoms making up the heterocycle are shared with another ring system. The heterocyclyl group can be attached to the rest of the molecule by a carbon or heteroatom; and, in the case where the heterocyclyl group is a bicyclic radical, the aforementioned attachment can be via a heteroatom-containing ring or a fused ring. Examples of heterocyclyl groups include, but are not limited to: azetidinyl, pyrrolidinyl, piperidinyl, azepanyl, diazepanyl, dihydrofuranyl (e.g., 2,3-dihydrofuranyl, 2,5-dihydrofuranyl), dioxolanyl, morpholinyl, oxazolidinyl, oxazinanyl, indolinyl, isoindolinyl, piperazinyl, tetrahydrofuranyl, thiomorpholinyl, dihydropyranyl (e.g., 3,4-dihydropyranyl, 3,6-dihydropyranyl), homopiperazinyl, dioxanyl, hexahydropyrimidinyl, pyrazolinyl, pyrazolidinyl, 4H-quinolizinyl, quinuclidinyl, tetrahydropyranyl, tetrahydropyridinyl, tetrahydropyrimidinyl, tetrahydrothiophenyl, thiazolidinyl, benzopyranyl, tetrahydroquinolinyl, dihydropyrrolopyridinyl, dihydrobenzoxazinyl, pyrrolopyridinyl, dihydronaphthridinyl, dihydroisoquinolinyl, and tetrahydroisoquinolinyl. Heterocyclylenyl is a subset of heterocyclyl, referring to the same residues as heterocyclyl, but with two points of attachment. As used herein, "heteroaryl" refers to a radical derived by the removal of one hydrogen atom from a 3- to 18-membered aromatic ring radical, containing 2 to 17 carbon atoms and from 1 to 6 heteroatoms selected from nitrogen, oxygen, and sulfur. As used herein, a heteroaryl group can be a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, wherein at least one ring in the ring system is completely unsaturated, i.e., contains a cyclic delocalized (4n+2) p-electron system according to Hückel theory. Heteroaryl groups include fused or bridged ring systems. In some embodiments, a heteroatom in a heteroaryl group is an oxidized heteroatom. In some embodiments, a heteroaryl group contains one or more nitrogen atoms. In some embodiments, one or more of the nitrogen atoms in a heteroaryl group is a quaternized nitrogen atom. A heteroaryl group is attached to the rest of the molecule through any ring atom. Examples of heteroaryl groups include, but are not limited to: azepinyl, acridinyl, benzimidazolyl, benzoindolyl, 1,3-benzodioxolyl, benzofuranyl, benzoxazolyl, benzo[d]thiazolyl, benzothiadiazolyl, benzo[b][l,4]dioxepinyl, benzo[b][l,4]oxazinyl, 1,4-benzodioxanyl, benzonaphthofuranyl, benzoxazolyl, benzodioxolyl, benzodioxinyl, benzopyranyl, benzopyranonyl, benzofuranyl, benzofuranonyl, benzothienyl, benzo-thieno[3,2-d]pyrimidinyl, benzotriazolyl, benzo[4,6]imidazo[l,2-a]pyridinyl, carbazolyl, cinnolinyl, cyclopenta[d]pyrimidinyl, 6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-d]pyrimidinyl, 5,6-dihydrobenzo[h]quinazolinyl, 5,6-dihydrobenzo[h]cinnolinyl, 6,7-dihydro-5H-benzo[6,7]cyclohepta[l,2-c]pyridazinyl, diphenfuranyl, diphenylthiophenyl, furanyl, furanonyl, furopyrido[3,2-c]pyridinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyrimidinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyridazinyl, 5,6,7,8,9,10-hexahydrocycloocta[d]pyridinyl, isothiazolyl, imidazolyl, indazolyl, indolyl, isoindolyl, dihydroindolyl, isoindolyl, indolizinyl, isoxazolyl, 5,8-methano-5,6,7,8-tetrahydroquinazolinyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]oxazinyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]dioxepinyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]dioxinyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]oxazolyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]thiazolyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]thiadiazolyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]cinnolinyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]pyridazinyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]pyridinyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]pyranyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]pyranonyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]furanyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]furanonyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]thienyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]thiophenyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]thieno[3,2-d]pyrimidinyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]thiadiazolyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]oxazolyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]thiazolyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]cinnolinyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]pyridazinyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]pyridinyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]pyranyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]pyranonyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]furanyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]furanonyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]thienyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]thiophenyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]thieno[3,2-d]pyrimidinyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]thiadiazolyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]oxazolyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]thiazolyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]cinnolinyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]pyridazinyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]pyridinyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]pyranyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]pyranonyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]furanyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]furanonyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]thienyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]thiophenyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]thieno[3,2-d]pyrimidinyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]thiadiazolyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]oxazolyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]thiazolyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]cinnolinyl, 5,6-methano-5,6-dihydrobenzo[b][l,4]pyridaz8-tetrahydroquinazolinyl), naphthyridinyl, 1,6-naphthyridinonyl, oxadiazolyl, 2-oxoazepinyl, oxazolyl, oxiranyl, 5,6,6a,7,8,9,10,10a-octahydrobenzo[H]quinazolinyl, 1-phenyl-1H-pyrrolyl, phenazinyl, phenothiazinyl, phenoxazinyl, phthalazinyl, pteridinyl, purinyl, pyrrolyl, pyrazolyl, pyrazolo[3,4-d]pyrimidinyl, pyridinyl, pyrido[3,2-d]pyrimidinyl, pyrido[3,4-d]pyrimidinyl, pyrazinyl, pyrimidinyl, pyridazinyl, pyrrolyl, quinazolinyl, quinoxalinyl, quinolinyl, tetrahydroquinolinyl, 5,6,7,8-tetrahydroquinazolinyl, 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinyl, 6,7,8,9-tetrahydro-5H-cyclohepta[4,5]thieno[2,3-d]pyrimidinyl, 5,6,7,8-tetrahydropyrido[4,5-c]pyridazinyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, triazinyl, thieno[2,3-d]pyrimidinyl, thieno[3,2-d]pyrimidinyl, thieno[2,3-c]pridinyl, and thiophenyl / thienyl. Heteroarylenyl is a subset of heteroaryl, referring to the same residues as heteroaryl, but with two points of attachment. In the foregoing or hereinafter, a “substituted” or “substituted” group, such as a substituted amino, substituted alkyl, or substituted aryl. Where not otherwise specified, a “substituted” or “substituted” group means that one or more hydrogen atoms in the group are replaced with one or more substituents. For example, a “substituted alkyl” means an alkyl group in which one or more hydrogen atoms are replaced with a substituent. Those skilled in the art will appreciate that various substituents can be included in the compounds useful in the present disclosure, as long as the introduction of the substituent does not affect the function of the present disclosure, as long as the purpose of the present disclosure can be achieved, it can be used in the present disclosure. In some embodiments, the substituent is selected from the group consisting of C1-C 10 alkyl, C6-C 10 aryl, C5-C 10 heteroaryl, C1-C 10 haloalkyl, -OC1-C 10 alkyl, OC1-C 10 alkylphenyl, -C1-C 10 alkyl-OH, -OC1-C 10haloalkyl, -SC1-C 10 alkyl, -SC1-C 10 alkyl, -SC1-C 10 alkyl-SH, -SC1-C 10 haloalkyl, halo substituent, -OH, -SH, -NH2, -C1-C 10 alkyl-NH2, -N(C1-C 10 alkyl)(C1-C 10 alkyl), -NH(C1-C 10 alkyl), N(C1-C 10 alkyl)(C1-C 10 alkyl), N(C1-C 10 alkyl), -CN, -NO2, -CO2H, -C(O)O(C1-C 10 alkyl), -CON(C1-C 10 alkyl)(C1-C 10 alkyl), -CONH(C1-C 10 alkyl), -CONH2, -NHC(O)(C1-C 10 alkyl), -NHC(O)(phenyl), -N(C1-C 10 alkyl)C(O)(C1-C 10 alkyl), -N(C1-C 10 alkyl)C(O)(phenyl), C(O)C1-C 10 alkyl, C(O)C1-C 10 alkyl, C(O)C1-C 10 haloalkyl, -OC(O)C1-C 10 alkyl, -SO2(C1-C 10 alkyl), -SO2(phenyl), -SO2(C1-C 10 haloalkyl), -SO2NH2, -SO2NH(C1-C 10 alkyl), -SO2NH(phenyl), -NHSO2(C1-C 10 alkyl), -NHSO2(phenyl), and -NHSO2(C1-C 10 haloalkyl). In some embodiments, the substituent is one of -C1-C3alkyl, -C6-C8aryl, -O-C1-C3alkyl, O-(C1-C3alkyl)phenyl, halo, -OH, -NH2, -CN, or -NO2. It will be understood by one skilled in the art that for any group containing one or more substituents, the group is not intended to introduce any substitution or substitution pattern that is not physically or synthetically realistic. Various hydroxyl protecting groups can be used in the present disclosure, such as the hydroxyl protecting groups or amino protecting groups. Generally, a protecting group renders a chemical functionality insensitive to particular reaction conditions, and can be added to and removed from that functionality in a molecule without substantially damaging the rest of the molecule. Representative hydroxyl protecting groups are disclosed in Peter G. M. Wuts, Greene’s Protective Groups in Organic Synthesis, Chapter 2, 5th edition, John Wiley & Sons, Inc., New Jersey, 2014, each of which is incorporated herein by reference in its entirety. In some embodiments, the protecting group is stable under basic conditions, but can be removed under acidic conditions. In some embodiments, nonexclusive examples of hydroxyl protecting groups that can be used herein include dimethoxytrityl (DMT), monomethoxytrityl, 9-phenylxanthyl (Pixyl), and 9-(p- methoxyphenyl)xanthyl (Mox). In some embodiments, nonexclusive examples of hydroxyl protecting groups that can be used herein include Tr (trityl), MMTr (4-methoxytrityl), DMTr (4,4'-dimethoxytrityl), and TMTr (4,4',4"-trimethoxytrityl). The term “subject,” as used herein, refers to any animal, such as a mammal or a marsupial. Subjects of the present disclosure include, but are not limited to, humans, non-human primates (e.g., rhesus or other types of macaques), mice, pigs, horses, donkeys, cows, rabbits, sheep, rats, and any species of poultry. As used herein, “treatment” refers to an approach for obtaining beneficial or desired results, including but not limited to therapeutic benefit. “Therapeutic benefit” means eradication or amelioration of the underlying disorder being treated. Also, a therapeutic benefit is achieved with the observation of improvement in a subject, even though the subject can still be afflicted with the underlying disorder, by eradicating or ameliorating one or more of the signs or symptoms of the underlying disorder. As used herein, "prevent" refers to an approach that results in a beneficial or desired result, including but not limited to prophylactic benefit. To obtain "prophylactic benefit", one or more of the single-stranded oligonucleotides, double-stranded oligonucleotides, pharmaceutical compositions and oligonucleotide conjugates of the present disclosure can be administered to a subject at risk of developing a disease associated with CFB mRNA, or to a subject reporting one or more physiological symptoms associated with the disease and CFB mRNA, even though a diagnosis of the disease can not have been made. In some embodiments, "prevention" includes reducing or eliminating the risk of a disease associated with CFB mRNA by administering a double-stranded oligonucleotide, a pharmaceutical composition or an oligonucleotide conjugate to a subject at risk of developing the disease associated with CFB mRNA before the risk of the disease progresses to an explicit disease process, intervening in the level of CFB mRNA or CFB protein, thereby reducing or eliminating the risk of the disease. Single-stranded oligonucleotide of the present disclosure In one aspect, the present disclosure provides a single-stranded oligonucleotide having a length of 16-30 nucleotides, the single-stranded oligonucleotide having a complementarity with CFB mRNA sufficient to mediate an RNAi effect; each nucleotide in the single-stranded oligonucleotide is a modified or unmodified nucleotide, wherein at least one nucleotide in the single-stranded oligonucleotide is a nucleotide X, at least one nucleotide is a fluorine-modified nucleotide; and, in the direction from the 5' end to the 3' end, at least one nucleotide X is located after the 8th nucleotide of the single-stranded oligonucleotide and is spaced apart from the 8th nucleotide by 4-7 nucleotides; And, in the direction from the 5' end to the 3' end, if the 14th nucleotide of the single-stranded oligonucleotide is a nucleotide X, and all nucleotides from the 15th nucleotide and thereafter of the single-stranded oligonucleotide are modified nucleotides, the 13th nucleotide of the single-stranded oligonucleotide is selected from one of an alkoxy-modified nucleotide, an alkyl-modified nucleotide, a substituted alkyl-modified nucleotide, an amine-modified nucleotide, a thermally unstable nucleotide and a BNA; Each nucleotide X is a deoxynucleotide or an unmodified nucleotide. In the present disclosure, diseases associated with the expression level of CFB mRNA and / or the level of CFB protein are treated or prevented by modulating the expression level of CFB mRNA and / or changing the level of the corresponding protein. The inventors have unexpectedly found that the single-stranded oligonucleotides, the double-stranded oligonucleotides comprising the single-stranded oligonucleotides as the antisense strand and the oligonucleotide conjugates of the present disclosure have good stability and CFB mRNA inhibitory activity in cells and / or in subjects, and thus have good application prospects. To exert the RNAi effect, the single-stranded oligonucleotide of the present disclosure has a length of 16 to 30 nucleotides. In some embodiments, the single-stranded oligonucleotide of the present disclosure has a length of 17 to 28, 19 to 26, or 20 to 24 nucleotides. In some embodiments, the single-stranded oligonucleotide of the present disclosure has a length of 19, 21, or 23 nucleotides. In this case, the single-stranded oligonucleotide of the present disclosure, the double-stranded oligonucleotide comprising the single-stranded oligonucleotide as an antisense strand, and the oligonucleotide conjugate have a better balance of synthesis cost, stability, and RNAi activity. In the single-stranded oligonucleotide of the present disclosure, at least one nucleotide X is located after the 8th nucleotide of the single-stranded oligonucleotide and is spaced apart from the 8th nucleotide of the single-stranded oligonucleotide by 4 to 7 nucleotides; and, in the direction from the 5' end to the 3' end, if the 14th nucleotide of the single-stranded oligonucleotide is a nucleotide X, and all of the nucleotides from the 15th nucleotide onward are modified nucleotides, then the 13th nucleotide of the single-stranded oligonucleotide is selected from one of an alkoxy-modified nucleotide, an alkyl-modified nucleotide, a substituted alkyl-modified nucleotide, an amine-modified nucleotide, a thermally unstable nucleotide, and a BNA. The inventors have particularly found that the single-stranded oligonucleotide of the present disclosure, by comprising a fluorine-modified nucleotide and a nucleotide X, can effectively maintain a high inhibitory activity of the single-stranded oligonucleotide, the double-stranded oligonucleotide, and the oligonucleotide conjugate against CFB mRNA while maintaining stability. In some embodiments, the number of nucleotides X in the single-stranded oligonucleotide is 1 to 3, for example, 1 or 2. In some embodiments, in the direction from the 5' end to the 3' end, each nucleotide X is located after the 8th nucleotide of the single-stranded oligonucleotide and is spaced apart from the 8th nucleotide of the single-stranded oligonucleotide by 3, 5, 7, or 10 nucleotides. In some embodiments, in the single-stranded oligonucleotide, each nucleotide X is located after the 8th nucleotide of the single-stranded oligonucleotide, and one of the nucleotides X is spaced apart from the 8th nucleotide by 5 nucleotides, i.e., in the direction from the 5' end to the 3' end, the 14th nucleotide of the single-stranded oligonucleotide is a nucleotide X. In some embodiments, there is only one nucleotide X in the single-stranded oligonucleotide, which is spaced 5 nucleotides from the 8th nucleotide in the single-stranded oligonucleotide in the 5' end to 3' end direction. In some embodiments, there are 2 nucleotides X in the single-stranded oligonucleotide, in which 1 nucleotide X is spaced 5 nucleotides from the 8th nucleotide in the single-stranded oligonucleotide in the 5' end to 3' end direction, and the other nucleotide X is spaced 3, 7, or 10 nucleotides from the 8th nucleotide in the single-stranded oligonucleotide in the 5' end to 3' end direction. In some embodiments, the 12th and 14th nucleotides, or the 14th and 16th nucleotides, or the 14th and 19th nucleotides in the single-stranded oligonucleotide in the 5' end to 3' end direction are nucleotides X. Each nucleotide X is independently selected from a deoxynucleotide or an unmodified nucleotide. In the present context, "unmodified nucleotide" refers to a ribonucleotide (RNA) in which both the base and the ribose are unmodified, i.e., the nucleotide base is a natural ribose base (one of A, U, C, G, T), and the 2' position of the nucleotide ribose is an unprotected hydroxyl group (2'-OH). Correspondingly, "modified nucleotide" refers to a nucleotide in which the base is modified, a nucleotide in which the hydroxyl group at the 2' position of the nucleotide ribose is replaced by another atom or group, or a nucleotide analog. In some embodiments, the 14th nucleotide or the 12th and 14th nucleotides in the single-stranded oligonucleotide in the 5' end to 3' end direction are deoxynucleotides, and the other nucleotides X are unmodified nucleotides. In some embodiments, the 14th nucleotide in the single-stranded oligonucleotide in the 5' end to 3' end direction is a deoxynucleotide, and the other nucleotides are modified nucleotides. In some embodiments, the number of modified nucleotides is more than 50%, more than 70%, or more than 85% of the total number of nucleotides in the single-stranded oligonucleotide of the present disclosure; or, the number of unmodified nucleotides in the single-stranded oligonucleotide is no more than 5, no more than 4, no more than 3, no more than 2, or no more than 1. In some embodiments, the number of unmodified nucleotides in the single-stranded oligonucleotide is 2 or 1. In some embodiments, each of the total number of nucleotides in the single-stranded oligonucleotide is independently a modified nucleotide. As described previously, the single-stranded oligonucleotide described in the present disclosure comprises, in addition to nucleotide X, fluorine-modified nucleotides. In some embodiments, the number of fluorine-modified nucleotides is 2-7. In some embodiments, the fluorine-modified nucleotides refer to 1 or 2 of the 2nd, 11th and 12th nucleotides, 1 or 2 of the 5th-7th nucleotides, and 0-2 of the 16th-19th nucleotides in the single-stranded oligonucleotide in the direction from the 5' end to the 3' end. In some embodiments, the fluorine-modified nucleotides refer to 2-5 of the 2nd, 5th, 6th, 7th, 12th, 16th, 18th and 19th nucleotides in the single-stranded oligonucleotide in the direction from the 5' end to the 3' end. In some embodiments, the fluorine-modified nucleotides refer to the 2nd and 6th nucleotides in the single-stranded oligonucleotide in the direction from the 5' end to the 3' end. In some embodiments, the fluorine-modified nucleotides refer to the 2nd, 6th and 16th nucleotides in the single-stranded oligonucleotide in the direction from the 5' end to the 3' end. In some embodiments, the fluorine-modified nucleotides refer to the 2nd, 5th, 7th, 12th and 16th nucleotides in the single-stranded oligonucleotide in the direction from the 5' end to the 3' end. In some embodiments, the fluorine-modified nucleotides refer to the 2nd, 7th, 12th, 16th and 19th nucleotides in the single-stranded oligonucleotide in the direction from the 5' end to the 3' end. In some embodiments, the fluorine-modified nucleotides refer to the 2nd, 6th, 12th, 16th and 19th nucleotides in the single-stranded oligonucleotide in the direction from the 5' end to the 3' end. In some embodiments, each modified nucleotide in the single-stranded oligonucleotide, except for nucleotide X and the fluorine-modified nucleotides, is independently selected from one of an alkoxy-modified nucleotide, a substituted alkoxy-modified nucleotide, an alkyl-modified nucleotide, a substituted alkyl-modified nucleotide, an amine-modified nucleotide, a thermally unstable nucleotide and a BNA. In the present context, "thermally unstable nucleotide" refers to a nucleotide having a thermally unstable modification, which is a modification that results in an oligonucleotide duplex having this modification having a thermal dissociation temperature that is at least 0.5 °C lower than an oligonucleotide duplex having an unmodified nucleotide at the corresponding position. Exemplary thermally unstable modifications can be found in the description of PCT publication WO2018 / 098328A1

[0236] -

[0251] The thermally unstable modification described in the paragraph. In some embodiments, the thermally unstable modification nucleotide is one of an acyclic nucleotide or an isonucleotide. Acyclic nucleotides are a class of nucleotides in which the sugar ring of the nucleotide is opened. In some embodiments, the acyclic nucleotide can be an unlocked nucleic acid (UNA) or a glycerol nucleic acid (GNA), wherein the UNA is as shown in Formula (15) and the GNA is as shown in Formula (16): In the above Formula (15) and Formula (16), R is selected from H, OH, or alkoxy (O-alkyl). Iso-nucleotides refer to compounds in which the position of the base on the ribose ring is changed. In some embodiments, the iso-nucleotide can be a compound in which the base is moved from the 1 '-position to the 2'-position or 3'-position on the ribose ring, as shown in Formula (17) or (18). In the above Formula (17)-(18) compounds, Base represents a nucleic acid base, such as A, U, G, C, or T; and R is selected from H, OH, F, or a non-fluoro group as described above. In some embodiments, the heat labile modified nucleotide is selected from one of 2'-OMe abasic nucleotide as shown in Formula (27B), 3'-OMe modified nucleotide as shown in Formula (27C), 5'-Me modified nucleotide as shown in Formula (27D), SNA as shown in Formula (27E), hGNA as shown in Formula (27F), hhGNA as shown in Formula (27G), mGNA as shown in Formula (27H), TNA as shown in Formula (27I), and h'GNA as shown in Formula (27J), UNA as shown in Formula (27K), or Hyp-spacer as shown in Formula (27L): In the above Formula (27A)-(27L) compounds, Base represents a nucleic acid base, such as A, U, G, C, or T; and R is selected from H, OH, F, alkoxy, alkyl, or alkoxy-substituted alkyl. 27 selected from H, OH, F, alkoxy, alkyl, or alkoxy-substituted alkyl. The * indicates that the carbon atom has chirality, and the compound can be in the R configuration, the S configuration, or a racemic mixture of the R and S configurations. In some embodiments, each heat labile modified nucleotide is independently a GNA as shown in Formula (27A). In the above context, BNA refers to a constrained or inaccessible nucleotide. The BNA can contain a five-, six-, or seven-membered ring bridged structure with a "fixed" C3'-endo sugar conformation. The bridge is typically incorporated at the 2'-, 4'-position of the ribose to provide a 2',4'-BNA nucleotide. In some embodiments, the BNA can be a LNA, an ENA, a cET BNA, etc., wherein the LNA is as shown in Formula (12), the ENA is as shown in Formula (13), and the cET BNA is as shown in Formula (14): In some embodiments, each modified nucleotide other than nucleotide X and the fluorinated nucleotide is selected from alkoxy-modified nucleotides, substituted alkoxy-modified nucleotides, or heat-labile nucleotides. In some embodiments, the number of heat-labile nucleotides in the single-chain oligonucleotide is 0-2. In some embodiments, the single-chain oligonucleotide does not contain any heat-labile nucleotides. In some embodiments, the number of heat-labile nucleotides in the single-chain oligonucleotide does not exceed 2. In some embodiments, the number of heat-labile nucleotides in the single-chain oligonucleotide is 1 or 2. In some embodiments, the single-chain oligonucleotide contains only 1 heat-labile nucleotide. In some embodiments, each modified nucleotide other than nucleotide X, the fluorinated nucleotide, and the heat-labile nucleotide is selected from alkoxy-modified nucleotides or substituted alkoxy-modified nucleotides. In some embodiments, for ease of synthesis, each alkoxy-modified nucleotide is a 2'-methoxy-modified nucleotide. 2'-methoxy-modified nucleotides (2'-OMe) are shown in formula (8). In some embodiments, 2'-amino-modified nucleotides (2'-NH2) are shown in formula (9). In some embodiments, 2'-deoxynucleotides (DNA) are shown in formula (10). In the compounds of formulas (7)-(10) and (12)-(14) above, Base represents a nucleic acid base, such as A, U, G, C or T. In the preceding and following text, “fluorinated nucleotides,” “2’-fluorinated nucleotides,” “nucleotides in which the 2’-hydroxyl group of the ribose group is replaced by fluorine,” and “nucleotides with a 2’-fluorinated ribose group” have the same meaning, all referring to compounds in which the 2’-hydroxyl group of the nucleotide is replaced by fluorine, resulting in compounds with the structure shown in formula (7); “methoxylated nucleotides,” “2’-methoxylated nucleotides,” “nucleotides in which the 2’-hydroxyl group of the ribose group is replaced by methoxyl,” and “nucleotides with a 2’-methoxy ribose group” have the same meaning, all referring to compounds in which the 2’-hydroxyl group of the ribose group of the nucleotide is replaced by methoxyl, resulting in compounds with the structure shown in formula (8). In some embodiments, the single stranded oligonucleotide of the present disclosure is 19-23 nucleotides in length and, in the 5' end to 3' end direction, the 14th nucleotide is a nucleotide X, 2 of the 5th-7th nucleotides and the 19th nucleotide and the 2nd, 12th and 16th nucleotides are fluorine-modified nucleotides, the 3rd nucleotide is an alkoxy-modified nucleotide or a substituted alkoxy-modified nucleotide, the 5th nucleotide is an alkoxy-modified nucleotide or a substituted alkoxy-modified nucleotide when it is not a fluorine-modified nucleotide, and each of the remaining nucleotides of the single stranded oligonucleotide is an alkoxy-modified nucleotide. In some embodiments, the single stranded oligonucleotide of the present disclosure is 19-23 nucleotides in length and, in the 5' end to 3' end direction, the 12th and 14th nucleotides are nucleotide X, the 2nd, 7th and 16th nucleotides are fluorine-modified nucleotides, the 3rd or 5th nucleotide is an alkoxy-modified nucleotide or a substituted alkoxy-modified nucleotide, and each of the remaining nucleotides of the single stranded oligonucleotide is an alkoxy-modified nucleotide. In some embodiments, the single stranded oligonucleotide of the present disclosure is 19-23 nucleotides in length and, in the 5' end to 3' end direction, the 14th nucleotide and the 16th nucleotide are nucleotide X, the 2nd and 6th nucleotides are fluorine-modified nucleotides, the 13th nucleotide is a substituted alkoxy-modified nucleotide or a BNA, the 3rd or 5th nucleotide is an alkoxy-modified nucleotide or a substituted alkoxy-modified nucleotide. In the 3' end to 5' end direction, 1 of the 1st-2nd nucleotides of the single stranded oligonucleotide is a thermally unstable nucleotide, and each of the remaining nucleotides of the single stranded oligonucleotide is an alkoxy-modified nucleotide. In some embodiments, the single stranded oligonucleotide of the present disclosure is 19-23 nucleotides in length and, in the 5' end to 3' end direction, one of the 16th-19th nucleotides and the 14th nucleotide is nucleotide X, the 2nd and 6th nucleotides are fluorine-modified nucleotides, the 16th nucleotide is a fluorine-modified nucleotide when it is not nucleotide X, the 13th nucleotide is a substituted alkoxy-modified nucleotide or a BNA, the 3rd or 5th nucleotide is an alkoxy-modified nucleotide or a substituted alkoxy-modified nucleotide, 0 nucleotides are an alkoxy-modified nucleotide or a thermally unstable nucleotide, and each of the remaining nucleotides of the single stranded oligonucleotide is an alkoxy-modified nucleotide. In some embodiments, the single stranded oligonucleotide is 21 nucleotides in length, wherein the 16th or 19th nucleotide and the 14th nucleotide are nucleotide X, and wherein the 14th nucleotide is a deoxynucleotide or an unmodified nucleotide, and the 16th or 19th nucleotide is an unmodified nucleotide. In some embodiments, the single stranded oligonucleotide of the present disclosure is 21 nucleotides in length and, in the 5' end to 3' end direction, the 14thnucleotide is a deoxy nucleotide, the 2nd, 5th, 7th, 12th, and 16thnucleotides are fluoro-modified nucleotides, the 3rdnucleotide is an alkoxy-modified nucleotide or a substituted alkoxy-modified nucleotide, and each of the remaining nucleotides of the single stranded oligonucleotide is an alkoxy-modified nucleotide. In some embodiments, the single stranded oligonucleotide of the present disclosure is 21 nucleotides in length and, in the 5' end to 3' end direction, the 14thnucleotide is a deoxy nucleotide, the 2nd, 7th, 12th, 16th, and 19thnucleotides are fluoro-modified nucleotides, and each of the remaining nucleotides of the single stranded oligonucleotide is an alkoxy-modified nucleotide. In some embodiments, the single stranded oligonucleotide of the present disclosure is 21 nucleotides in length and, in the 5' end to 3' end direction, the 14thnucleotide is a deoxy nucleotide, the 2nd, 6th, 12th, 16th, and 19thnucleotides are fluoro-modified nucleotides, and each of the remaining nucleotides of the single stranded oligonucleotide is an alkoxy-modified nucleotide. In some embodiments, the single stranded oligonucleotide of the present disclosure is 21 nucleotides in length and, in the 5' end to 3' end direction, the 12thand 14thnucleotides are deoxy nucleotides, the 2nd, 7th, and 16thnucleotides are fluoro-modified nucleotides, and each of the remaining nucleotides of the single stranded oligonucleotide is an alkoxy-modified nucleotide. In some embodiments, the single stranded oligonucleotide of the present disclosure is 21 nucleotides in length and, in the 5' end to 3' end direction, the 14thnucleotide is a deoxy nucleotide, the 16thnucleotide is an unmodified nucleotide, the 2ndand 6thnucleotides are fluoro-modified nucleotides, the 13thnucleotide is a substituted alkoxy-modified nucleotide, the 2ndnucleotide of the single stranded oligonucleotide is a thermally unstable nucleotide in the 3' end to 5' end direction, and each of the remaining nucleotides of the single stranded oligonucleotide is an alkoxy-modified nucleotide. In some embodiments, the single stranded oligonucleotide of the present disclosure is 21 nucleotides in length and, in the 5' end to 3' end direction, the 14thnucleotide is a deoxy nucleotide, the 19thnucleotide is an unmodified nucleotide, the 2nd, 6th, and 16thnucleotides are fluoro-modified nucleotides, the 13thnucleotide is a substituted alkoxy-modified nucleotide, and each of the remaining nucleotides of the single stranded oligonucleotide is an alkoxy-modified nucleotide. In some embodiments, each nucleotide X in the single stranded oligonucleotide of the present disclosure refers to a deoxynucleotide. In some embodiments, each alkoxy-modified nucleotide in the single stranded oligonucleotide of the present disclosure refers to a methoxy-modified nucleotide. In some embodiments, each substituted alkoxy-modified nucleotide in the single stranded oligonucleotide of the present disclosure refers to a 2'-0-methoxyethyl-modified nucleotide. In some embodiments, each BNA in the single stranded oligonucleotide of the present disclosure refers to a LNA or a cET BNA. In some embodiments, each thermally unstable modified nucleotide in the single stranded oligonucleotide of the present disclosure refers to a GNA. In some embodiments, each of at least 2 of the linking groups between adjacent nucleotides in the single stranded oligonucleotide of the present disclosure independently is a phosphorothioate group with a modification group. In some embodiments, each of 1-4 of the linking groups between adjacent nucleotides in the first 5 nucleotides at the 5' end in the single stranded oligonucleotide of the present disclosure independently is a phosphorothioate group with a modification group. In some embodiments, each of 1-4 of the linking groups between adjacent nucleotides in the first 5 nucleotides at the 3' end in the single stranded oligonucleotide of the present disclosure independently is a phosphorothioate group with a modification group. In some embodiments, each of 2 of the linking groups between adjacent nucleotides in the first 3 nucleotides at the 5' end or 4 of the linking groups between adjacent nucleotides in the first 5 nucleotides at the 5' end in the single stranded oligonucleotide of the present disclosure independently is a phosphorothioate group with a modification group. In some embodiments, each of 2 of the linking groups between adjacent nucleotides in the first 3 nucleotides at the 3' end or 4 of the linking groups between adjacent nucleotides in the first 5 nucleotides at the 3' end in the single stranded oligonucleotide of the present disclosure independently is a phosphorothioate group with a modification group. In some embodiments, if there is an unmodified nucleotide in the single stranded oligonucleotide of the present disclosure, each of 1 or both of the 2 linking groups between the unmodified nucleotide and the adjacent nucleotides independently is a phosphorothioate group with a modification group. The modified phosphorothioate group can make the single stranded oligonucleotide of the present disclosure better resistant to exonuclease, enhancing the stability of the oligonucleotide in a subject. In some embodiments, at least 2, or each of 2-6, of the linking groups between adjacent nucleotides in the single stranded oligonucleotide of the present disclosure are independently phosphodiester groups with a modification group. In some embodiments, each of 2-6 of the linking groups between adjacent nucleotides in the single stranded oligonucleotide are independently phosphodiester groups with a modification group. In some embodiments, each of 3 or 4 of the linking groups between adjacent nucleotides in the single stranded oligonucleotide are independently phosphodiester groups with a modification group. In some embodiments, each of the linking groups between adjacent nucleotides in the first 1-3 nucleotides at the 5' end, and the first 1-3 nucleotides at the 3' end of the single stranded oligonucleotide are independently phosphodiester groups with a modification group. In some embodiments, if there is an unmodified nucleotide in the single stranded oligonucleotide, each of the unmodified nucleotide and one or both of the two linking groups between the unmodified nucleotide and the adjacent nucleotides are independently phosphodiester groups with a modification group. In some embodiments, the phosphodiester group with a modification group is a phosphorothioate group having a structure as shown in formula (28): In some embodiments, the 5' terminal nucleotide of the single stranded oligonucleotide is a 5'-hydroxyl nucleotide having a structure as shown in formula (29), a 5'-phosphate nucleotide having a structure as shown in formula (30), or a 5'-phosphate analog modified nucleotide having a structure selected from one of formula (31) - formula (34): wherein R is selected from one of H, OH, OCH3, and F; Base represents a nucleic acid base selected from A, U, C, G, or T. In some embodiments, the 5'-phosphate nucleotide is a 5'-phosphate modified nucleotide as shown in formula (30), the 5'-phosphate analog modified nucleotide is a 5'-(E)-vinylphosphonate (E-VP) modified nucleotide as shown in formula (31), or a phosphorothioate modified nucleotide as shown in formula (33). In some embodiments, the 5' terminal nucleotide of the single stranded oligonucleotide is a 5'-hydroxyl nucleotide or a 5'-(E)-vinylphosphonate (E-VP) modified nucleotide. In some embodiments, the 5' terminal nucleotide is a 5'-(E)-vinylphosphonate (E-VP) modified nucleotide, which can further increase one or more of the stability, the pharmacodynamic activity in a subject, and the long-acting property of the single stranded oligonucleotide, the double stranded oligonucleotide comprising the single stranded oligonucleotide, and the oligonucleotide conjugate of the present disclosure. In some embodiments, the single-stranded oligonucleotide is 21 nucleotides in length, and in the 5' end to 3' end direction, the 14thnucleotide is a deoxyribonucleotide, the 2nd, 5th, 7th, 12th, and 16thnucleotides are fluorinated modified nucleotides, the 3rdnucleotide is a methoxy modified nucleotide, each of the remaining nucleotides in the single-stranded oligonucleotide is a methoxy modified nucleotide, the linking group between any two adjacent nucleotides of the 1stto 3rdnucleotides at the 5' end and the linking group between any two adjacent nucleotides of the 1stto 3rdnucleotides at the 3' end are phosphorothioate groups; and the 5' end nucleotide is a 5'-hydroxyl nucleotide of Formula (29) or a 5'-vinylphosphonate modified nucleotide of Formula (31). As previously described, the single-stranded oligonucleotide of the present disclosure has sufficient complementarity to the CFB mRNA to mediate an RNAi effect. In some embodiments, the single-stranded oligonucleotide of the present disclosure is substantially complementary to the CFB mRNA. In the context of the present disclosure, "substantially complementary" means that the single-stranded oligonucleotide of the present disclosure has sufficient complementarity to the CFB mRNA such that the single-stranded oligonucleotide reduces or eliminates the production of the protein encoded by the CFB mRNA through an RNAi effect. In some embodiments, "substantially complementary" means that the single-stranded oligonucleotide of the present disclosure is substantially reverse complementary, essentially reverse complementary, or completely reverse complementary to the CFB mRNA over a length of at least 16 nucleotides, for example, over a length of 16-25 nucleotides, over a length of 18-23 nucleotides, or over a length of 19-21 nucleotides. In some embodiments, the single-stranded oligonucleotide of the present disclosure is completely reverse complementary to the CFB mRNA. In the preceding and following text, "at least partially anticomplementary," "substantially anticomplementary," "truly anticomplementary," and "completely anticomplementary" can be used to refer to the base pairing between two single-stranded nucleotide sequences: between a single-stranded oligonucleotide and CFB mRNA, between the sense and antisense strands of a double-stranded oligonucleotide (such as siRNA), and between the antisense strand of a double-stranded oligonucleotide and CFB mRNA. Unless otherwise specified, "at least partially anticomplementary" means that within a given length of nucleotide sequence, there are no more than 50% base mismatches between the two nucleotide sequences; "substantially anticomplementary" means that within a given length of nucleotide sequence, there are no more than 3 base mismatches between the two nucleotide sequences; "truly anticomplementary" means that within a given length of nucleotide sequence, there are 1 base mismatch between the two nucleotide sequences; and "completely anticomplementary" means that within a given length of nucleotide sequence, there are no base mismatches between the two nucleotide sequences. When two nucleotide sequences are completely anticomplementary within a given length of nucleotide sequence, they can anneal to form a double-stranded hybrid uniquely composed of Watson-Crick base pairs within the given length of nucleotide sequence. Unless otherwise stated, when referring to a shorter nucleotide sequence as "completely anticomplementary" to a longer nucleotide sequence, it means that the two nucleotide sequences are completely anticomplementary over the entire length of the shorter nucleotide sequence. For example, the complete anticomplementary relationship between a single-stranded oligonucleotide and CFB mRNA described in this disclosure means that the single-stranded oligonucleotide is completely anticomplementary over its entire length; in other words, the single-stranded oligonucleotide can form a double-stranded hybrid by each nucleotide uniquely forming a Watson-Crick base pair with a nucleotide on the CFB mRNA. In some embodiments, the two "fully complementary" nucleotide sequences may include completely anticomplementary internal regions (e.g., completely anticomplementary across a length of at least 6, 8, or 10 nucleotides). In some embodiments, the single-stranded oligonucleotides of this disclosure are completely anticomplementary to CFB mRNA at least within a seed region. The "seed region" refers to the region of nucleotides 2-8 of the single-stranded oligonucleotide of this disclosure, where the single-stranded oligonucleotide of this disclosure can better mediate RNAi and suppress CFB mRNA levels. In some embodiments, the single-stranded oligonucleotide is substantially or completely complementary to the CFB mRNA over a stretch of at least 16 nucleotides. In some embodiments, the nucleotide sequence of positions 2-19 of the single-stranded oligonucleotide is completely complementary to the CFB mRNA, in the 5' end to 3' end direction. In some embodiments, the nucleotide sequence of the single-stranded oligonucleotide, except for the first position of the 5' end, is completely complementary to the CFB mRNA, in the 5' end to 3' end direction. In some embodiments, all of the nucleotides of the single-stranded oligonucleotide are completely complementary to the CFB mRNA. In some embodiments, the single-stranded oligonucleotide of the present disclosure can be the first, second, third, or fourth single-stranded oligonucleotide described below, each of which is described herein. The first single-stranded oligonucleotide In some embodiments, the present disclosure provides a first single-stranded oligonucleotide. The single-stranded oligonucleotide contains a nucleotide sequence II, which is equal in length to the nucleotide sequence set forth in SEQ ID NO: 2, and has no more than 3 base differences: 5'-Z2GACAUCCAGAUAAUCCUC-3' (SEQ ID NO: 2), wherein Z2 is A or U, and the nucleotide sequence II contains a nucleotide Z'2 at a position corresponding to Z2, which is the first nucleotide at the 5' end of the single-stranded oligonucleotide sequence. In the foregoing and hereinafter of the present disclosure, "corresponding to a position" means being at the same position in a nucleotide sequence, counting from the same end of the nucleotide sequence, for example, the first nucleotide at the 5' end of the nucleotide sequence II is the nucleotide corresponding to the first nucleotide of SEQ ID NO: 2. In some embodiments, there are no more than 1 base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 2. The base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 2 can include a difference at the Z'2 position and / or a base difference at any other nucleotide position in the nucleotide sequence II. In some embodiments, the base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 2 can include a difference at the Z'2 position and / or a base difference at a nucleotide position adjacent to Z'2. In some embodiments, there is no base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 2. In some embodiments, the base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 2 comprises a difference at position Z'2, and Z'2 is selected from C, U, or G. In some embodiments, the base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 2 is a difference at position Z'2, and Z'2 is selected from C, U, or G. In some embodiments, the single-stranded oligonucleotide further comprises a nucleotide sequence IV, which is linked to the 3' end of the nucleotide sequence II, has a length of 1, 2, 3, or 4 nucleotides, each nucleotide in the nucleotide sequence IV is independently one of the non-fluoro-modified nucleotides, the nucleotide sequence IV is substantially reverse-complementary or fully reverse-complementary to the CFB mRNA, and each of the non-fluoro-modified nucleotides is independently selected from one of 2'-methoxy-modified nucleotide, 2'-alkyl-modified nucleotide having an alkyl group of carbon number 1-3, 2'-amino-modified nucleotide, 2'-substituted amino-modified nucleotide, and heat-unstable nucleotide. In some embodiments, the nucleotide sequence IV has a length of 2 nucleotides. In some embodiments, the nucleotide sequence IV has a length of 1 nucleotide, and the base is C; or, the nucleotide sequence IV has a length of 2 nucleotides, and the base composition is CC from 5' end to 3' end; or, the nucleotide sequence IV has a length of 3 nucleotides, and the base composition is CCU from 5' end to 3' end; or, the nucleotide sequence IV has a length of 4 nucleotides, and the base composition is CCUU from 5' end to 3' end. In some embodiments, the single-stranded oligonucleotide of the present disclosure further comprises a nucleotide sequence V, each nucleotide in the nucleotide sequence V is independently a non-fluoro-modified nucleotide, the nucleotide sequence V has a length of 1-3 nucleotides, and is linked to the 3' end of the nucleotide sequence IV or the nucleotide sequence II; after the single-stranded oligonucleotide forms a double-stranded oligonucleotide with a sense strand, the nucleotide sequence V constitutes a 3' overhang end of an antisense strand of the double-stranded oligonucleotide. In some embodiments, the nucleotide sequence V of the present disclosure has a length of 2 nucleotides, and from 5' end to 3' end, the nucleotide sequence V is 2 consecutive thymine deoxynucleotides, 2 consecutive uracil nucleotides, or is fully reverse-complementary to the CFB mRNA. In some embodiments, the nucleotide sequence V in the present disclosure is linked to the 3' end of the nucleotide sequence II, and from 5' end to 3' end, the base composition of the nucleotide sequence V is UU or CC. In some embodiments, the single-stranded oligonucleotide comprises only nucleotide sequence II and nucleotide sequence V, nucleotide sequence II consists of SEQ ID NO: 2, and nucleotide sequence V has a base composition of CC. The second single-stranded oligonucleotide In some embodiments, the single-stranded oligonucleotide of the present disclosure is the second single-stranded oligonucleotide. In some embodiments, the single-stranded oligonucleotide contains nucleotide sequence II, which is equal in length to the nucleotide sequence set forth in SEQ ID NO: 4, and differs from the nucleotide sequence set forth in SEQ ID NO: 4 by no more than 3 bases: 5'-Z4UCCAGAUAAUCCUCCCUU-3' (SEQ ID NO: 4), wherein Z4 is A or U, and nucleotide sequence II contains a nucleotide Z'4 at a position corresponding to Z4, which is the first nucleotide at the 5' end of the single-stranded oligonucleotide sequence. In some embodiments, the nucleotide sequence II differs from the nucleotide sequence set forth in SEQ ID NO: 4 by no more than 1 base. The base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 4 can include a difference at the Z'4 position and / or a base difference at any other nucleotide position in nucleotide sequence II. In some embodiments, the base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 4 can include a base difference at the Z'4 position and / or at a nucleotide position adjacent to Z'4. In some embodiments, there is no base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 4. In some embodiments, the base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 4 includes a difference at the Z'4 position, and Z'4 is selected from C, U, or G. In some embodiments, the base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 4 is a difference at the Z'4 position, and Z'4 is selected from C, U, or G. In some embodiments, the single-stranded oligonucleotide further comprises a nucleotide sequence IV, which is linked to the 3' end of the nucleotide sequence II, has a length of 1, 2, 3, or 4 nucleotides, each nucleotide in the nucleotide sequence IV is independently one of the non-fluoro-modified nucleotides, the nucleotide sequence IV is substantially reverse-complementary or fully reverse-complementary to the CFB mRNA, and each of the non-fluoro-modified nucleotides is independently selected from one of 2'-methoxy-modified nucleotide, 2'-alkyl-modified nucleotide having an alkyl group of 1-3 carbon atoms, 2'-amino-modified nucleotide, 2'-substituted amino-modified nucleotide, and heat-unstable nucleotide. In some embodiments, the nucleotide sequence IV has a length of 2 nucleotides. In some embodiments, the nucleotide sequence IV has a length of 1 nucleotide, and the base is G; or, the nucleotide sequence IV has a length of 2 nucleotides, and the base composition is GG from the 5' end to the 3' end; or, the nucleotide sequence IV has a length of 3 nucleotides, and the base composition is GGG from the 5' end to the 3' end; or, the nucleotide sequence IV has a length of 4 nucleotides, and the base composition is GGGA from the 5' end to the 3' end. In some embodiments, the single-stranded oligonucleotide of the present disclosure further comprises a nucleotide sequence V, each nucleotide in the nucleotide sequence V is independently a non-fluoro-modified nucleotide, the nucleotide sequence V has a length of 1-3 nucleotides, and is linked to the 3' end of the nucleotide sequence IV or the nucleotide sequence II; after the single-stranded oligonucleotide forms a double-stranded oligonucleotide with the sense strand, the nucleotide sequence V constitutes the 3' overhang end of the antisense strand of the double-stranded oligonucleotide. In some embodiments, the nucleotide sequence V of the present disclosure has a length of 2 nucleotides, and from the 5' end to the 3' end, the nucleotide sequence V is 2 consecutive thymine deoxynucleotides, 2 consecutive uracil nucleotides, or is fully reverse-complementary to the CFB mRNA. In some embodiments, the nucleotide sequence V in the present disclosure is linked to the 3' end of the nucleotide sequence II, and from the 5' end to the 3' end, the base composition of the nucleotide sequence V is UU or GG. In some embodiments, the single-stranded oligonucleotide comprises only the nucleotide sequence II and the nucleotide sequence V, the nucleotide sequence II consists of SEQ ID NO: 4, and the base composition of the nucleotide sequence V is GG. A third single-stranded oligonucleotide In some embodiments, the single-stranded oligonucleotide of the present disclosure is a third single-stranded oligonucleotide. In some embodiments, the single-stranded oligonucleotide comprises a nucleotide sequence II, wherein the nucleotide sequence II is equal in length to the nucleotide sequence set forth in SEQ ID NO: 6 and differs by no more than 3 bases from the nucleotide sequence set forth in SEQ ID NO: 6: 5'-Z6UCACUCACAUUGUAGUAG-3' (SEQ ID NO: 6), wherein Z6 is A or U, the nucleotide sequence II comprises a nucleotide Z'6 at a position corresponding to Z6, and Z'6 is the first nucleotide at the 5' end of the single-stranded oligonucleotide sequence. In some embodiments, the nucleotide sequence II differs by no more than 1 base from the nucleotide sequence set forth in SEQ ID NO: 6. The base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 6 can include a difference at the Z'6 position and / or a base difference at any other nucleotide position in the nucleotide sequence II. In some embodiments, the base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 6 can include a base difference at the Z'6 position and / or at a nucleotide position adjacent to Z'6. In some embodiments, there is no base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 6. In some embodiments, the base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 6 includes a difference at the Z'6 position, and Z'6 is selected from C, U, or G. In some embodiments, the base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 6 is a difference at the Z'6 position, and Z'6 is selected from C, U, or G. In some embodiments, the single-stranded oligonucleotide further comprises a nucleotide sequence IV, which is linked to the 3' end of the nucleotide sequence II, has a length of 1, 2, 3, or 4 nucleotides, each nucleotide in the nucleotide sequence IV is independently one of non-fluoro-modified nucleotides, the nucleotide sequence IV is substantially reverse-complementary or fully reverse-complementary to CFB mRNA, and each of the non-fluoro-modified nucleotides is independently selected from one of 2'-methoxy-modified nucleotides, 2'-alkyl-modified nucleotides having an alkyl group of 1-3 carbon atoms, 2'-amino-modified nucleotides, 2'-substituted amino-modified nucleotides, and heat unstable nucleotides. In some embodiments, the nucleotide sequence IV has a length of 2 nucleotides. In some embodiments, the nucleotide sequence IV has a length of 1 nucleotide, and the base is G; or, the nucleotide sequence IV has a length of 2 nucleotides, and the base composition is GG from 5' end to 3' end; or, the nucleotide sequence IV has a length of 3 nucleotides, and the base composition is GGA from 5' end to 3' end; or, the nucleotide sequence IV has a length of 4 nucleotides, and the base composition is GGAU from 5' end to 3' end. In some embodiments, the single-stranded oligonucleotide of the present disclosure further contains a nucleotide sequence V, each nucleotide of the nucleotide sequence V is independently a non-fluorinated modified nucleotide, the nucleotide sequence V has a length of 1 to 3 nucleotides, and is linked to the 3' end of the nucleotide sequence IV or the nucleotide sequence II; after the single-stranded oligonucleotide forms a double-stranded oligonucleotide with the sense strand, the nucleotide sequence V constitutes the 3' overhang end of the antisense strand of the double-stranded oligonucleotide. In some embodiments, the nucleotide sequence V of the present disclosure has a length of 2 nucleotides, and from 5' end to 3' end, the nucleotide sequence V is 2 consecutive thymine deoxynucleotides, 2 consecutive uracil nucleotides, or is fully reverse complementary to the CFB mRNA. In some embodiments, the nucleotide sequence V in the present disclosure is linked to the 3' end of the nucleotide sequence II, and from 5' end to 3' end, the base composition of the nucleotide sequence V is UU or GG. In some embodiments, the single-stranded oligonucleotide only contains the nucleotide sequence II and the nucleotide sequence V, the nucleotide sequence II consists of SEQ ID NO: 6, and the base composition of the nucleotide sequence V is GG. The fourth single-stranded oligonucleotide In some embodiments, the single-stranded oligonucleotide of the present disclosure is the fourth single-stranded oligonucleotide. The single-stranded oligonucleotide contains a nucleotide sequence II, the nucleotide sequence II has a length equal to the nucleotide sequence shown in SEQ ID NO: 8, and has no more than 3 base differences: 5'-Z8GUGGAAAGAGAUCUCAUC-3' (SEQ ID NO: 8), wherein Z8 is A or U, the nucleotide sequence II contains a nucleotide Z'8 at the position corresponding to Z8, and Z'8 is the first nucleotide at the 5' end of the single-stranded oligonucleotide sequence. In some embodiments, the nucleotide sequence II differs from the nucleotide sequence set forth in SEQ ID NO: 8 by no more than 1 base. The base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 8 can include a difference at the Z'8 position and / or a base difference at any other nucleotide position in the nucleotide sequence II. In some embodiments, the base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 8 can include a base difference at the Z'8 position and / or a base difference at a nucleotide position adjacent to Z'8. In some embodiments, the nucleotide sequence II is identical to the nucleotide sequence set forth in SEQ ID NO: 8. In some embodiments, the base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 8 includes a difference at the Z'8 position, and Z'8 is selected from C, U, or G. In some embodiments, the base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 8 is a difference at the Z'8 position, and Z'8 is selected from C, U, or G. In some embodiments, the single-stranded oligonucleotide further comprises a nucleotide sequence IV linked to the 3' end of the nucleotide sequence II, the nucleotide sequence IV having a length of 1, 2, 3, or 4 nucleotides, each nucleotide in the nucleotide sequence IV being independently one of a non-fluoro-modified nucleotide, the nucleotide sequence IV being substantially reverse-complementary or fully reverse-complementary to CFB mRNA, each of the non-fluoro-modified nucleotide being independently selected from one of a 2'-methoxy-modified nucleotide, a 2'-alkyl-modified nucleotide having an alkyl group having a carbon number of 1-3, a 2'-amino-modified nucleotide, a 2'-substituted amino-modified nucleotide, and a thermally unstable nucleotide. In some embodiments, the nucleotide sequence IV has a length of 2 nucleotides. In some embodiments, the nucleotide sequence IV has a length of 1 nucleotide, and the base is A; or, the nucleotide sequence IV has a length of 2 nucleotides, and the base composition is ACU in the 5' end to 3' end direction; or, the nucleotide sequence IV has a length of 3 nucleotides, and the base composition is ACU in the 5' end to 3' end direction; or, the nucleotide sequence IV has a length of 4 nucleotides, and the base composition is ACUC in the 5' end to 3' end direction. In some embodiments, the single-stranded oligonucleotide of the present disclosure further contains a nucleotide sequence V, each nucleotide of the nucleotide sequence V is independently a non-fluorinated modified nucleotide, the nucleotide sequence V has a length of 1 to 3 nucleotides, is linked to the 3' end of the nucleotide sequence IV or the nucleotide sequence II; after the single-stranded oligonucleotide forms a double-stranded oligonucleotide with the sense strand, the nucleotide sequence V constitutes the 3' overhang end of the antisense strand of the double-stranded oligonucleotide. In some embodiments, the nucleotide sequence V of the present disclosure has a length of 2 nucleotides, and in the direction from the 5' end to the 3' end, the nucleotide sequence V is 2 consecutive thymine deoxynucleotides, 2 consecutive uracil nucleotides, or is fully reverse complementary to the CFB mRNA. In some embodiments, the nucleotide sequence V in the present disclosure is linked to the 3' end of the nucleotide sequence II, and in the direction from the 5' end to the 3' end, the base composition of the nucleotide sequence V is UU or AC. In some embodiments, the single-stranded oligonucleotide only contains the nucleotide sequence II and the nucleotide sequence V, the nucleotide sequence II consists of SEQ ID NO: 8, and the base composition of the nucleotide sequence V is AC. The fifth single-stranded oligonucleotide In some embodiments, the present disclosure provides a fifth single-stranded oligonucleotide. Wherein, the single-stranded oligonucleotide contains a nucleotide sequence II, the nucleotide sequence II is equal in length to the nucleotide sequence shown in SEQ ID NO: 74, and has no more than 3 base differences: 5'-Z 10 UGAUGUAGACCUCCUUCC-3' (SEQ ID NO: 74), Wherein, Z 10 is A or U, the nucleotide Z' 10 in the nucleotide sequence II corresponds to the position of Z 10 , and Z' 10 is the first nucleotide at the 5' end of the single-stranded oligonucleotide sequence. In some embodiments, there are no more than 1 base difference between the nucleotide sequence II and the nucleotide sequence shown in SEQ ID NO: 74. The base difference between the nucleotide sequence II and the nucleotide sequence shown in SEQ ID NO: 74 can include the difference at the position of Z' 10 and / or the base difference at any other nucleotide position in the nucleotide sequence II. In some embodiments, the base difference between the nucleotide sequence II and the nucleotide sequence shown in SEQ ID NO: 74 can include the difference at the position of Z' 10 and / or Z' 10a base difference at the nucleotide position. In some embodiments, there is no base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 74. In some embodiments, the base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 74 comprises Z 10 a difference at the position, and Z 10 is selected from C, A, or G. In some embodiments, the base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 74 is Z 10 a difference at the position, and Z 10 is selected from C, A, or G. In some embodiments, the single-stranded oligonucleotide further comprises a nucleotide sequence IV, which is linked to the 3' end of the nucleotide sequence II, has a length of 1, 2, 3, or 4 nucleotides, each nucleotide in the nucleotide sequence IV is independently one of non-fluoro-modified nucleotides, the nucleotide sequence IV is substantially reverse-complementary or fully reverse-complementary to CFB mRNA, and each of the non-fluoro-modified nucleotides is independently selected from one of 2'-methoxy-modified nucleotides, 2'-alkyl-modified nucleotides having an alkyl group of 1-3 carbon atoms, 2'-amino-modified nucleotides, 2'-substituted amino-modified nucleotides, and heat unstable nucleotides. In some embodiments, the nucleotide sequence IV has a length of 2 nucleotides. In some embodiments, the nucleotide sequence IV has a length of 1 nucleotide, and the base is G; or, the nucleotide sequence IV has a length of 2 nucleotides, and the base composition is GA in the direction from the 5' end to the 3' end; or, the nucleotide sequence IV has a length of 3 nucleotides, and the base composition is GAG in the direction from the 5' end to the 3' end; or, the nucleotide sequence IV has a length of 4 nucleotides, and the base composition is GAGU in the direction from the 5' end to the 3' end. In some embodiments, the single-stranded oligonucleotide of the present disclosure further comprises a nucleotide sequence V, each nucleotide in the nucleotide sequence V is independently a non-fluoro-modified nucleotide, the nucleotide sequence V has a length of 1-3 nucleotides, and is linked to the 3' end of the nucleotide sequence IV or the nucleotide sequence II; after the single-stranded oligonucleotide forms a double-stranded oligonucleotide with a sense strand, the nucleotide sequence V constitutes a 3' overhang end of the antisense strand of the double-stranded oligonucleotide. In some embodiments, the nucleotide sequence V of the present disclosure has a length of 2 nucleotides, and in the direction from the 5' end to the 3' end, the nucleotide sequence V is 2 consecutive thymine deoxynucleotides, 2 consecutive uracil nucleotides, or is fully reverse-complementary to CFB mRNA. In some embodiments, the nucleotide sequence V in the present disclosure is linked at the 3' end of the nucleotide sequence II, and the base composition of the nucleotide sequence V is UU or GA, in the direction from the 5' end to the 3' end. In some embodiments, the single-stranded oligonucleotide comprises only the nucleotide sequence II and the nucleotide sequence V, the nucleotide sequence II consists of SEQ ID NO: 74, and the base composition of the nucleotide sequence V is GA. A sixth single-stranded oligonucleotide In some embodiments, the single-stranded oligonucleotide of the present disclosure is the sixth single-stranded oligonucleotide. Wherein the single-stranded oligonucleotide contains a nucleotide sequence II, the nucleotide sequence II is equal in length to the nucleotide sequence set forth in SEQ ID NO: 76, and has no more than 3 base differences from the nucleotide sequence set forth in SEQ ID NO: 76: 5'-Z 12 UGAUGUGAAAGUCUCGGG-3' (SEQ ID NO: 76), wherein Z 12 is A or U, the nucleotide sequence II comprises a nucleotide Z' 12 at a position corresponding to Z 12 , and Z' 12 is the first nucleotide at the 5' end of the single-stranded oligonucleotide sequence. In some embodiments, the nucleotide sequence II has no more than 1 base difference from the nucleotide sequence set forth in SEQ ID NO: 76. The base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 76 can include a difference at the Z' 12 position and / or a base difference at any other nucleotide position in the nucleotide sequence II. In some embodiments, the base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 76 can include a difference at the Z' 12 position and / or a base difference at the adjacent nucleotide position of Z' 12 . In some embodiments, the nucleotide sequence II has no base difference from the nucleotide sequence set forth in SEQ ID NO: 76. In some embodiments, the base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 76 includes a difference at the Z' 12 position, and Z' 12 is selected from C, U or G. In some embodiments, the base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 76 is a difference at the Z' 12 position, and Z' 12 is selected from C, U or G. In some embodiments, the single-stranded oligonucleotide further comprises a nucleotide sequence IV, which is linked to the 3' end of the nucleotide sequence II, has a length of 1, 2, 3, or 4 nucleotides, each nucleotide in the nucleotide sequence IV is independently one of the non-fluoro-modified nucleotides, the nucleotide sequence IV is substantially or completely reverse-complementary to the CFB mRNA, and each of the non-fluoro-modified nucleotides is independently selected from one of 2'-methoxy-modified nucleotide, 2'-alkyl-modified nucleotide having an alkyl group of 1-3 carbon atoms, 2'-amino-modified nucleotide, 2'-substituted amino-modified nucleotide, and heat unstable nucleotide. In some embodiments, the nucleotide sequence IV has a length of 2 nucleotides. In some embodiments, the nucleotide sequence IV has a length of 1 nucleotide, and the base is C; or, the nucleotide sequence IV has a length of 2 nucleotides, and the base composition is CG from 5' end to 3' end; or, the nucleotide sequence IV has a length of 3 nucleotides, and the base composition is CGU from 5' end to 3' end; or, the nucleotide sequence IV has a length of 4 nucleotides, and the base composition is CGUG from 5' end to 3' end. In some embodiments, the single-stranded oligonucleotide of the present disclosure further comprises a nucleotide sequence V, each nucleotide in the nucleotide sequence V is independently a non-fluoro-modified nucleotide, the nucleotide sequence V has a length of 1-3 nucleotides, and is linked to the 3' end of the nucleotide sequence IV or the nucleotide sequence II; after the single-stranded oligonucleotide forms a double-stranded oligonucleotide with the sense strand, the nucleotide sequence V constitutes the 3' overhang end of the antisense strand of the double-stranded oligonucleotide. In some embodiments, the nucleotide sequence V of the present disclosure has a length of 2 nucleotides, and from 5' end to 3' end, the nucleotide sequence V is 2 consecutive thymine deoxynucleotides, 2 consecutive uracil nucleotides, or is completely reverse-complementary to the CFB mRNA. In some embodiments, the nucleotide sequence V in the present disclosure is linked to the 3' end of the nucleotide sequence II, and from 5' end to 3' end, the base composition of the nucleotide sequence V is UU or CG. In some embodiments, the single-stranded oligonucleotide comprises only the nucleotide sequence II and the nucleotide sequence V, the nucleotide sequence II consists of SEQ ID NO: 76, and the base composition of the nucleotide sequence V is CG. In some embodiments, the single-stranded oligonucleotide is an antisense strand of any one of siRNAa1, siRNAb1, siRNAc1, siRNAd1, siRNAe1, or siRNAf1 shown in Table 1; or the single-stranded oligonucleotide is an antisense strand of any one of Conjugate 1-Conjugate 44 shown in Table 2A. In some embodiments, the single-stranded oligonucleotide of the present disclosure can independently exert a pharmacodynamic activity. In some embodiments, the single-stranded oligonucleotide of the present disclosure is an antisense oligonucleotide (ASO). In some embodiments, the single-stranded oligonucleotide of the present disclosure is a single-stranded RNAi (ssRNAi) compound. In some embodiments, the single-stranded oligonucleotide of the present disclosure exerts a pharmacodynamic activity as one single strand (e.g., an antisense strand) of a double-stranded oligonucleotide. The double-stranded oligonucleotide of the present disclosure In another aspect, the present disclosure also provides a double-stranded oligonucleotide comprising an antisense strand of the present disclosure, the double-stranded oligonucleotide containing a sense strand and an antisense strand, each nucleotide in the sense strand being a modified or unmodified nucleotide, the sense strand and the antisense strand being at least partially reverse complementary to form a double-stranded region, wherein the antisense strand is a single-stranded oligonucleotide as described in the present disclosure above. In the double-stranded oligonucleotide of the present disclosure, the length of the sense strand and the antisense strand is 19-26 nucleotides. In some embodiments, the length of the antisense strand is not less than the length of the sense strand. In some embodiments, the length of the sense strand is 19-23 nucleotides. Thus, the ratio of the length of the sense strand and the antisense strand of the double-stranded oligonucleotide of the present disclosure can be 19 / 19, 19 / 20, 19 / 21, 19 / 22, 20 / 20, 20 / 21, 20 / 22, 20 / 23, 21 / 21, 21 / 22, 21 / 23, 21 / 24, 22 / 22, 22 / 23, 22 / 24, 22 / 25, 23 / 23, 23 / 24, 23 / 25, or 23 / 26. In some embodiments, for the sake of synthesis convenience, the length of the sense strand is 19-21 nucleotides, and the length of the antisense strand is 19-23 nucleotides. In some embodiments, the length of the sense strand and the antisense strand is the same, both being 19, 20, or 21 nucleotides; or the length of the sense strand is 19 nucleotides, and the length of the antisense strand is 20-24 nucleotides; or the length of the sense strand is 20 nucleotides, and the length of the antisense strand is 21-24 nucleotides; or the length of the sense strand is 21 nucleotides, and the length of the antisense strand is 22-24 nucleotides. In some embodiments, in the sense strand of the double-stranded oligonucleotide of the present disclosure, 2-3 of the 11th-13th nucleotides from the 3' end to the 5' end are fluorine-modified nucleotides, the 1st and / or the last nucleotide of the sense strand is an alkoxy-modified nucleotide or an inverted abasic deoxyribonucleotide (abbreviated as invab or ia, having a structure as shown in formula (35)), and the nucleotides at the remaining positions are non-fluorine-modified nucleotides, each of which is independently selected from one of an alkoxy-modified nucleotide, an alkyl-modified nucleotide, an amine-modified nucleotide, and a thermally unstable nucleotide. In some embodiments, the oxygen atom shown in formula (35) directly connected to the ribose ring can be connected to the 3' phosphate group of the 3' penultimate nucleotide of the sense strand. In some embodiments, the oxygen atom shown in formula (35) directly connected to the ribose ring can be connected to the 3' phosphate group of the 3' terminal nucleotide of the sense strand, and the oxygen atom shown in formula (35) connected to the ribose ring by methylene can be connected to a hydrogen atom, a hydroxyl protecting group, or a delivery group described below. In some embodiments, the oxygen atom shown in formula (35) connected to the ribose ring by methylene can be connected to the 5' phosphate group of the 5' penultimate nucleotide of the sense strand. In some embodiments, the oxygen atom shown in formula (35) connected to the ribose ring by methylene is connected to the 5' phosphate group of the 5' penultimate nucleotide of the sense strand, and the oxygen atom shown in formula (35) directly connected to the ribose ring can be connected to a hydrogen atom, a hydroxyl protecting group, or a delivery group described below. In some embodiments, the sense strand comprises 19-21 nucleotides, and the antisense strand comprises 21-23 nucleotides. In some embodiments, in the sense strand of the double-stranded oligonucleotide of the present disclosure, 2-3 of the 11th-13th nucleotides from the 3' end to the 5' end are fluorine-modified nucleotides, the 1st and / or the last nucleotide of the sense strand is an alkoxy-modified nucleotide or an inverted abasic deoxyribonucleotide, and the nucleotides at the remaining positions are all alkoxy-modified nucleotides. At this time, through the position matching of the modified nucleotides of the sense strand and the antisense strand, the double-stranded oligonucleotide of the present disclosure has better stability and / or activity of forming a RISC complex, thereby showing stable and efficient APOC3 mRNA inhibitory activity. In some embodiments, each of the alkoxy-modified nucleotides is a methoxy-modified nucleotide. In some embodiments, in the sense strand, at least one of the linking groups linking two adjacent nucleotides is a phosphate group with a modification group, which is present between two adjacent nucleotides in the 1stto 5thnucleotides at the 5' terminal end and between two adjacent nucleotides in the 1stto 5thnucleotides at the 3' terminal end of the sense strand. At this time, the double-stranded oligonucleotide of the present disclosure has the ability to resist nucleic acid exonuclease and good balance of CFB mRNA, thereby having high efficient CFB mRNA inhibitory activity while improving stability. In some embodiments, 1 to 4 of the linking groups between adjacent nucleotides in the 1stto 5thnucleotides at the 5' terminal end and / or 1 to 4 of the linking groups between adjacent nucleotides in the 1stto 5thnucleotides at the 3' terminal end of the sense strand are each independently a phosphate group with a modification group. In some embodiments, all 4 of the linking groups between adjacent nucleotides in the 1stto 5thnucleotides at the 5' terminal end of the sense strand are each independently a phosphate group with a modification group. In some embodiments, all 4 of the linking groups between adjacent nucleotides in the 1stto 5thnucleotides at the 3' terminal end of the sense strand are each independently a phosphate group with a modification group. In some embodiments, the linking groups linking two adjacent nucleotides in the 1stto 3rd, 1stto 4th, or 1stto 5thnucleotides at the 5' and / or 3' terminal end of the sense strand are phosphate groups with a modification group. In some embodiments, the linking groups between adjacent nucleotides in the 1stto 3rdnucleotides at the 5' terminal end of the sense strand are phosphate groups with a modification group. The definition and selection range of the phosphate group with a modification group are the same as described above for the phosphate group with a modification group in the antisense strand of the present disclosure. In some embodiments, each phosphate group with a modification group is a phosphorothioate group having a structure as shown in formula (28). In some embodiments, the sense strand is the sense strand of any one of siRNAal, siRNAb 1, siRNAcl, siRNAdl, siRNAel or siRNAfl shown in Table 1, or the sense strand of any one of Conjugate 1-Conjugate 44 shown in Table 2A. In some embodiments, the sense strand comprises 19-21 nucleotides, the antisense strand comprises 21-23 nucleotides; in the sense strand, the 11th and 13th nucleotides, or the 11th-13th nucleotides, from the 3' end to the 5' end are fluoro-modified nucleotides, the 1st nucleotide and / or the last nucleotide of the sense strand is an alkoxy-modified nucleotide or an inverted abasic deoxynucleotide, and the remaining nucleotides are alkoxy-modified nucleotides; 1-4 of the linking groups between adjacent nucleotides in the 1st-5th nucleotides from the 5' end of the sense strand, and / or 1-4 of the linking groups between adjacent nucleotides in the 1st-5th nucleotides from the 3' end of the sense strand, are each independently phosphates having a modification group. In some embodiments, the linking group between every two adjacent nucleotides in the 1st-2nd, 1st-3rd, 1st-4th, or 1st-5th nucleotides from the 5' end and / or the 3' end of the sense strand are phosphates having a modification group, and the remaining adjacent nucleotides in the sense strand are linked by phosphates. In some embodiments, the linking group between every two adjacent nucleotides in the 1st-3rd, 1st-4th, or 1st-5th nucleotides from the 5' end of the sense strand are phosphates having a modification group, and the remaining adjacent nucleotides in the sense strand are linked by phosphates. In some embodiments, the linking group between every two adjacent nucleotides in the 1st-2nd, 1st-3rd, 1st-4th, or 1st-5th nucleotides from the 3' end of the sense strand are phosphates having a modification group, and the remaining adjacent nucleotides in the sense strand are linked by phosphates. In some embodiments, all adjacent nucleotides in the sense strand are linked by phosphates. In some embodiments, the phosphate having a modification group is a phosphorothioate group having the structure shown in formula (28), and the alkoxy-modified nucleotide is a 2'-methoxy-modified nucleotide. In some embodiments, in the double-stranded oligonucleotide of the present disclosure, the sense strand comprises 19-21 nucleotides, and the antisense strand comprises 21-23 nucleotides; in the sense strand, the 11th and 13th nucleotides from the 3' end to the 5' end are fluorine-modified nucleotides, the 1st nucleotide is an inverted abasic deoxynucleotide, and the remaining nucleotides are methoxy-modified nucleotides; 1-4 of the linking groups between adjacent nucleotides in the 1st-3rd nucleotides from the 5' end of the sense strand and / or the linking groups between adjacent nucleotides in the 1st-3rd nucleotides from the 3' end of the sense strand are phosphates with a modification group; in the antisense strand, the 14th nucleotide from the 5' end to the 3' end is a deoxynucleotide, the 2nd, 5th, 7th, 12th and 16th nucleotides are fluorine-modified nucleotides, the 3rd nucleotide is an alkoxy-modified nucleotide or a substituted alkoxy-modified nucleotide, and each of the remaining nucleotides in the antisense strand is an alkoxy-modified nucleotide. In some embodiments, the 14th nucleotide from the 5' end to the 3' end is a deoxynucleotide, the 2nd, 7th, 12th, 16th and 19th nucleotides are fluorine-modified nucleotides, and each of the remaining nucleotides in the antisense strand is an alkoxy-modified nucleotide. In some embodiments, the 14th nucleotide from the 5' end to the 3' end is a deoxynucleotide, the 2nd, 6th, 12th, 16th and 19th nucleotides are fluorine-modified nucleotides, and each of the remaining nucleotides in the antisense strand is an alkoxy-modified nucleotide. In some embodiments, the 12th and 14th nucleotides from the 5' end to the 3' end are deoxynucleotides, the 2nd, 7th and 16th nucleotides are fluorine-modified nucleotides, and each of the remaining nucleotides in the antisense strand is an alkoxy-modified nucleotide; in the antisense strand, the linking groups between two adjacent nucleotides in the 1st-3rd nucleotides from the 5' end and the linking groups between two adjacent nucleotides in the 1st-3rd nucleotides from the 3' end of the antisense strand are phosphates with a modification group, and if there are unmodified nucleotides, 1-2 of the 2 linking groups between each of the unmodified nucleotides and the adjacent nucleotides are phosphates with a modification group. In some embodiments, the 5' terminal nucleotide of the antisense strand is a 5'-hydroxyl nucleotide represented by formula (29) or a 5'-vinyl phosphate-modified nucleotide represented by formula (31). In some embodiments, the sense strand comprises 19 nucleotides, and the antisense strand comprises 21 nucleotides; in the sense strand, the 11th and 13th nucleotides from the 3' end to the 5' end are fluorine-modified nucleotides, the 1st nucleotide is an inverted deoxy- nucleotide, and the remaining nucleotides are methoxy-modified nucleotides; the linkage between the adjacent nucleotides in the 1st-3rd nucleotides at the 5' end of the sense strand is a phosphorothioate linkage; in the antisense strand, the 14th nucleotide from the 5' end to the 3' end is a deoxy-nucleotide, the 2nd, 5th, 7th, 12th and 16th nucleotides are fluorine-modified nucleotides, and each of the remaining nucleotides in the antisense strand is a methoxy-modified nucleotide; the linkage between the adjacent nucleotides in the 1st-3rd nucleotides at the 5' end of the antisense strand and the linkage between the adjacent nucleotides in the 1st-3rd nucleotides at the 3' end of the antisense strand are phosphorothioate linkages; and the 5' terminal nucleotide of the antisense strand is a 5'-hydroxyl nucleotide represented by formula (29) or a 5'-vinylphosphonate-modified nucleotide represented by formula (31). The double-stranded oligonucleotide of the present disclosure can achieve a good balance between CFB mRNA expression regulation activity and in vivo stability by having the above-mentioned modification scheme. In the context of the present disclosure, the "modification scheme" refers to a combination of different numbers, positions, and types of nucleotide ribose modifications, phosphate modifications, 5' end modifications, and / or base modifications that are not or weakly related to a specific sequence. In some embodiments, the double-stranded oligonucleotide of the present disclosure can achieve a good balance between CFB mRNA expression regulation activity and in vivo stability by having the above-mentioned modification scheme, while maintaining excellent stability without significantly reducing the original pharmaceutical activity of the double-stranded oligonucleotide. In some embodiments, the double-stranded oligonucleotide of the present disclosure is an siRNA, and the double-stranded oligonucleotide of the present disclosure can achieve a good balance between CFB mRNA inhibition activity and in vivo stability by having the above-mentioned modification scheme, while maintaining excellent stability without significantly reducing the original RNAi activity of the siRNA. In some embodiments, the double-stranded oligonucleotide of the present disclosure consists of a double-stranded region that is substantially reverse complementary or completely reverse complementary, and one or two overhanging ends of the sense strand and / or one or two overhanging ends of the antisense strand. In some embodiments, the double-stranded oligonucleotide of the present disclosure consists of a double-stranded region that is substantially reverse complementary or completely reverse complementary, and one overhanging end of the antisense strand. In the context of the present disclosure, a "double-stranded region" is a double-stranded structure formed between the shortest nucleotide sequence of all base-paired bases and all base mismatches between base-paired bases on each single strand in a double-stranded nucleic acid structure. Thus, a double-stranded region consists of all base pairs and all base mismatches between base pairs in a double-stranded nucleic acid structure. In some embodiments, the number of base mismatches is no more than 20%, 15%, 10%, or 5% of the total number of base pairs forming the double-stranded region. In some embodiments, the number of base mismatches in a double-stranded region is no more than 3, no more than 2, or no more than 1. In some embodiments, a double-stranded nucleic acid structure includes a double-stranded region and one or more overhanging ends consisting of unpaired nucleotides on one or both single strands. In some embodiments, a double-stranded nucleic acid structure includes only a double-stranded region. In some embodiments, the sense strand and the antisense strand form a double-stranded region spanning at least 16 nucleotide positions, i.e., the double-stranded region formed by the sense strand and the antisense strand includes at least 16 base pairs. In the context of the present disclosure, each base pair forming a double-stranded region is independently complementary or mismatched. In some embodiments, the sense strand and the antisense strand form a double-stranded region spanning 16-23 nucleotide positions, i.e., the double-stranded region formed by the sense strand and the antisense strand includes 16-23 base pairs. In some embodiments, the sense strand and the antisense strand form a double-stranded region spanning 18, 19, 20, or 21 nucleotide positions, i.e., the double-stranded region formed by the sense strand and the antisense strand includes 18, 19, 20, or 21 base pairs. In some embodiments, the sense strand and the antisense strand are substantially or completely reverse complementary within the double-stranded region. In some embodiments, the sense strand and the antisense strand of a double-stranded oligonucleotide of the present disclosure are substantially or completely reverse complementary in their entire nucleotide length. In some embodiments, the number of base differences between the sense strand and the CFB mRNA is no more than 3, or no more than 2, or no more than 1. In some embodiments, there is no base difference between the sense strand and the CFB mRNA. In the foregoing and hereinafter, a nucleotide sequence and another nucleotide sequence have a "base difference" if the base type of a nucleotide at the same position in the former is different from that in the latter, e.g., if the base type of a nucleotide in the latter is A, and the base type of a corresponding nucleotide in the former is U, C, G, or T, then the two nucleotide sequences are considered to have a base difference at that position. When a base is modified, as long as the modified base does not affect the purine-pyrimidine pairing relationship when forming the double-stranded nucleic acid structure described above, the modified base and the original base are considered to have no base difference. In some embodiments, U and T are considered to have no base difference. In some embodiments, C and 5-methylcytosine (5mC) are considered to have no base difference. In some embodiments, a nucleotide at a position is replaced with an abasic nucleotide or an equivalent thereof, and the replacement is considered to result in a base difference at that position. When aligning two nucleotide sequences to determine the number of base differences, the alignment is performed in a manner that has the least number of base differences among all possible alignments, and the base differences are determined based on the alignment. In this case, "the same position" refers to the corresponding position between the two nucleotide sequences in the alignment. For example, when nucleotide sequence A positions 1-5 are aligned with nucleotide sequence B positions 2-6 in the same direction, and the number of base differences is the least compared to other alignments, then "the same position" refers to nucleotide sequence A position 1 aligned with nucleotide sequence B position 2, nucleotide sequence A position 2 aligned with nucleotide sequence B position 3, and so on. In some embodiments, the number of base differences between two nucleotide sequences of different lengths is the total number of base differences between the first nucleotide to the last nucleotide of the shorter nucleotide sequence and each corresponding nucleotide of the other nucleotide sequence, in the same orientation. In some embodiments, the number of base differences between two nucleotide sequences of the same length is the total number of base differences between the first nucleotide to the last nucleotide of either nucleotide sequence and the first nucleotide to the last nucleotide of the other nucleotide sequence, in the same orientation. In some embodiments, the absence of base differences between two nucleotide sequences of different lengths is the absence of base differences between the first nucleotide to the last nucleotide of the shorter nucleotide sequence and each corresponding nucleotide of the other nucleotide sequence, in the same orientation. In some embodiments, the absence of base differences between two nucleotide sequences of the same length is the absence of base differences between the first nucleotide to the last nucleotide of one nucleotide sequence and the first nucleotide to the last nucleotide of the other nucleotide sequence, in the same orientation. The double-stranded oligonucleotide of the present disclosure can be various double-stranded oligonucleotides that modulate CFB mRNA. In some embodiments, it can be a double-stranded oligonucleotide that inhibits or down-regulates CFB mRNA, such as siRNA; in some embodiments, it can be a double-stranded oligonucleotide that activates or up-regulates CFB mRNA, such as saRNA. In some embodiments, the double-stranded oligonucleotide is siRNA. In some embodiments, the double-stranded oligonucleotide of the present disclosure can be the following first-sixth double-stranded oligonucleotides, each of which is described below. First double-stranded oligonucleotide In some embodiments, the present disclosure provides a first double-stranded oligonucleotide. The first double-stranded oligonucleotide contains a sense strand and an antisense strand, the sense strand contains a nucleotide sequence I that is equal in length to the nucleotide sequence set forth in SEQ ID NO: 1 with no more than 3 base differences, and the nucleotide sequence II that is equal in length to the nucleotide sequence set forth in SEQ ID NO: 2 with no more than 3 base differences: 5'-GAGGAUUAUCUGGAUGUCZ1-3' (SEQ ID NO: 1) 5'-Z2GACAUCCAGAUAAUCCUC-3' (SEQ ID NO: 2); wherein Z1 is U, A, or an inverted abasic deoxy nucleotide (ia), Z2 is A or U, the nucleotide sequence I comprises a nucleotide Z'1 at a position corresponding to Z1, the nucleotide sequence II comprises a nucleotide Z'2 at a position corresponding to Z2, and Z'2 is the first nucleotide at the 5' end of the single-stranded oligonucleotide sequence. In some embodiments, the sense strand comprises only the nucleotide sequence I, and the antisense strand comprises only the nucleotide sequence II. In some embodiments, there is no more than 1 base difference between the nucleotide sequence I and the nucleotide sequence set forth in SEQ ID NO: 1, and / or no more than 1 base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 2. In some embodiments, the base difference between the nucleotide sequence I and the nucleotide sequence set forth in SEQ ID NO: 1 can include a difference at the Z'1 position and / or a base difference at any other nucleotide position in the nucleotide sequence I. In some embodiments, the base difference between the nucleotide sequence I and the nucleotide sequence set forth in SEQ ID NO: 1 can include a base difference at the Z'1 position and / or at a nucleotide position adjacent to Z'1. In some embodiments, the base difference between the nucleotide sequence I and the nucleotide sequence set forth in SEQ ID NO: 1 is a base difference at the Z'1 position, preferably, Z'1 is an inverted abasic deoxy nucleotide. In some embodiments, the difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 2 includes a difference at the Z'2 position, and Z'2 is selected from C, U, or G. In some embodiments, the difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 2 is a difference at the Z'2 position, and Z'2 is selected from C, U, or G. In some embodiments, the nucleotide at position 2-19 of the nucleotide sequence II is fully reverse complementary to the CFB mRNA in the direction from 5' end to 3' end. In some embodiments, the nucleotide sequence II is fully reverse complementary to the nucleotide sequence I. In some embodiments, the 2nd nucleotide in the nucleotide sequence II in the direction from 5' end to 3' end and the 2nd nucleotide in the nucleotide sequence I in the direction from 3' end to 5' end have a base mismatch. By including the base mismatch, one can have a higher CFB mRNA inhibitory activity while maintaining a low off-target effect. In some embodiments, the sense strand further comprises a nucleotide sequence III, the anti-sense strand further comprises a nucleotide sequence IV, the nucleotide sequence III has a length of 1, 2, 3, or 4 nucleotides, the nucleotide sequence IV and the nucleotide sequence III have equal length, and the nucleotide sequence IV and the nucleotide sequence III are substantially reverse complementary or fully reverse complementary, and the nucleotide sequence III is linked to the 5' end of the nucleotide sequence I. In some embodiments, the nucleotide sequence III and the nucleotide sequence IV each has a length of 1 nucleotide, the nucleotide sequence III has a base of G, and the nucleotide sequence IV has a base of C, in the 5' to 3' direction; or the nucleotide sequence III and the nucleotide sequence IV each has a length of 2 nucleotides, the nucleotide sequence III has a base composition of GG, and the nucleotide sequence IV has a base composition of CC, in the 5' end to 3' end direction; or the nucleotide sequence III and the nucleotide sequence IV each has a length of 3 nucleotides, the nucleotide sequence III has a base composition of AGG, and the nucleotide sequence IV has a base composition of CCU, in the 5' end to 3' end direction; or the nucleotide sequence III and the nucleotide sequence IV each has a length of 4 nucleotides, the nucleotide sequence III has a base composition of AAGG, and the nucleotide sequence IV has a base composition of CCUU, in the 5' end to 3' end direction. In some embodiments, the nucleotide sequence III and the nucleotide sequence IV each has a length of 2 nucleotides, the nucleotide sequence III has a base composition of GG, and the nucleotide sequence IV has a base composition of CC, in the 5' end to 3' end direction. In some embodiments, the anti-sense strand further comprises a nucleotide sequence V, each nucleotide of the nucleotide sequence V is independently a non-fluorinated modified nucleotide, the nucleotide sequence V has a length of 1 to 3 nucleotides, is linked to the 3' end of the nucleotide sequence IV or the nucleotide sequence II, and forms a 3' overhang end of the anti-sense strand after forming the double-stranded oligonucleotide. In some embodiments, the nucleotide sequence V has a length of 2 nucleotides, and in the 5' end to 3' end direction, the nucleotide sequence V is two consecutive thymine deoxyribonucleotides, two consecutive uracil ribonucleotides, or fully reverse complementary to the CFB mRNA. In some embodiments, the nucleotide sequence V is linked to the 3' end of the nucleotide sequence II, and in the 5' end to 3' end direction, the base composition of the nucleotide sequence V is selected from CC or UU. In some embodiments, the sense strand comprises only the nucleotide sequence I, the antisense strand comprises only the nucleotide sequence II and the nucleotide sequence V, the nucleotide sequence II consists of SEQ ID NO: 2, the nucleotide sequence I consists of SEQ ID NO: 1, and the nucleotide sequence V is linked at the 3' end of the nucleotide sequence II, and the base composition of the nucleotide sequence V, in the 5' end to 3' end direction, is CC. The second double-stranded oligonucleotide In some embodiments, the present disclosure provides a second double-stranded oligonucleotide. The second double-stranded oligonucleotide contains a sense strand and an antisense strand, the sense strand contains a nucleotide sequence I, the nucleotide sequence I is equal in length to the nucleotide sequence set forth in SEQ ID NO: 3, and differs by no more than 3 bases, the nucleotide sequence II is equal in length to the nucleotide sequence set forth in SEQ ID NO: 4, and differs by no more than 3 bases: 5'-AAGGGAGGAUUAUCUGGAZ3-3' (SEQ ID NO: 3) 5'-Z4UCCAGAUAAUCCUCCCUU-3' (SEQ ID NO: 4); wherein Z3 is U, A or inverted abasic deoxynucleotide, Z4 is A or U, the nucleotide sequence I comprises a nucleotide Z'3 at a position corresponding to Z3, the nucleotide sequence II comprises a nucleotide Z'4 at a position corresponding to Z4, and the Z'4 is the first nucleotide at the 5' end of the single-stranded oligonucleotide sequence. In some embodiments, the sense strand comprises only the nucleotide sequence I, and the antisense strand comprises only the nucleotide sequence II. In some embodiments, there is no more than 1 base difference between the nucleotide sequence I and the nucleotide sequence set forth in SEQ ID NO: 3, and / or no more than 1 base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 4. In some embodiments, the base difference between the nucleotide sequence I and the nucleotide sequence set forth in SEQ ID NO: 3 can include a difference at the Z'3 position and / or a base difference at any other nucleotide position in the nucleotide sequence I. In some embodiments, the base difference between the nucleotide sequence I and the nucleotide sequence set forth in SEQ ID NO: 3 can include a difference at the Z'3 position and / or a difference at a nucleotide position adjacent to Z'3. In some embodiments, the base difference between the nucleotide sequence I and the nucleotide sequence set forth in SEQ ID NO: 3 is a difference at the Z'3 position, and preferably, Z'3 is an inverted abasic deoxynucleotide. In some embodiments, the difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 4 comprises a difference at position Z'4, and Z'4 is selected from C, U, or G. In some embodiments, the difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 4 is a difference at position Z'4, and Z'4 is selected from C, U, or G. In some embodiments, the nucleotide sequence II is fully reverse-complemented to the nucleotide sequence I. In some embodiments, the 2ndnucleotide in the nucleotide sequence II in the 5' end to 3' end direction is base-mismatched to the 2ndnucleotide in the nucleotide sequence I in the 3' end to 5' end direction. By including this base-mismatch, one can have a higher CFB mRNA inhibitory activity while maintaining a low off-target effect. In some embodiments, the sense strand further comprises a nucleotide sequence III, the antisense strand further comprises a nucleotide sequence IV, the nucleotide sequence III has a length of 1, 2, 3, or 4 nucleotides, the nucleotide sequence IV and the nucleotide sequence III have an equal length, and the nucleotide sequence IV and the nucleotide sequence III are substantially reverse-complemented or fully reverse-complemented, and the nucleotide sequence III is linked to the 5' end of the nucleotide sequence I. In some embodiments, the length of the nucleotide sequence III and the nucleotide sequence IV is 1 nucleotide, the base of the nucleotide sequence III is C, and the base of the nucleotide sequence IV is G, in the 5' to 3' direction; in this case, the length ratio of the sense strand to the antisense strand is 20 / 20; or the length of the nucleotide sequence III and IV is 2 nucleotides, the base composition of the nucleotide sequence III is CC, and the base composition of the nucleotide sequence IV is GG, in the 5' end to 3' end direction; in this case, the length ratio of the sense strand to the antisense strand is 21 / 21; or the length of the nucleotide sequence III and IV is 3 nucleotides, the base composition of the nucleotide sequence III is CCC, and the base composition of the nucleotide sequence IV is GGG, in the 5' end to 3' end direction; in this case, the length ratio of the sense strand to the antisense strand is 22 / 22; or the length of the nucleotide sequence III and IV is 4 nucleotides, the base composition of the nucleotide sequence III is ACCC, and the base composition of the nucleotide sequence IV is GGGA, in the 5' end to 3' end direction; in this case, the length ratio of the sense strand to the antisense strand is 23 / 23. In some embodiments, the length of the nucleotide sequence III and the nucleotide sequence IV is 2 nucleotides, the base composition of the nucleotide sequence III is CC, and the base composition of the nucleotide sequence IV is GG, in the 5' end to 3' end direction; in this case, the length ratio of the sense strand to the antisense strand is 21 / 21. In some embodiments, the antisense strand further comprises a nucleotide sequence V, each nucleotide of the nucleotide sequence V is independently a non-fluorinated modified nucleotide, the length of the nucleotide sequence V is 1 to 3 nucleotides, and the nucleotide sequence V is linked to the 3' end of the nucleotide sequence IV or the nucleotide sequence II, forming a 3' overhang end of the antisense strand after forming the double-stranded oligonucleotide. In some embodiments, the length of the nucleotide sequence V is 2 nucleotides, and the nucleotide sequence V is 2 consecutive thymine deoxynucleotides, 2 consecutive uracil nucleotides, or fully reverse complementary to the CFB mRNA, in the 5' end to 3' end direction. In some embodiments, the nucleotide sequence V is linked to the 3' end of the nucleotide sequence II, and the base composition of the nucleotide sequence V is selected from GG or UU, in the 5' end to 3' end direction. In some embodiments, the sense strand only comprises the nucleotide sequence I, the antisense strand only comprises the nucleotide sequence II and the nucleotide sequence V, the nucleotide sequence II consists of SEQ ID NO: 4, the nucleotide sequence I consists of SEQ ID NO: 3, the nucleotide sequence V is linked to the 3' end of the nucleotide sequence II, and the base composition of the nucleotide sequence V is GG, in the 5' end to 3' end direction. A third double-stranded oligonucleotide In some embodiments, the present disclosure also provides a third double- stranded oligonucleotide. The third double-stranded oligonucleotide comprises a sense strand and an antisense strand, the sense strand comprises a nucleotide sequence I which is identical in length to the nucleotide sequence set forth in SEQ ID NO: 5, and differs by no more than 3 bases, and the nucleotide sequence II which is identical in length to the nucleotide sequence set forth in SEQ ID NO: 6, and differs by no more than 3 bases: 5'-CUACUACAAUGUGAGUGAZ5-3' (SEQ ID NO: 5) 5'-Z6UCACUCACAUUGUAGUAG-3' (SEQ ID NO: 6); wherein Z5 is U, A or inverted abasic deoxynucleotide, Z6 is A or U, Z'5 is a nucleotide in the nucleotide sequence I at a position corresponding to Z5, Z'6 is a nucleotide in the nucleotide sequence II at a position corresponding to Z6, and Z'6 is the first nucleotide at the 5' end of the single-stranded oligonucleotide sequence. In some embodiments, the sense strand comprises only the nucleotide sequence I, and the antisense strand comprises only the nucleotide sequence II. In some embodiments, the nucleotide sequence I differs by no more than 1 base from the nucleotide sequence set forth in SEQ ID NO: 5, and / or the nucleotide sequence II differs by no more than 1 base from the nucleotide sequence set forth in SEQ ID NO: 6. In some embodiments, the base difference between the nucleotide sequence I and the nucleotide sequence set forth in SEQ ID NO: 5 can include a difference at the Z'5 position and / or a base difference at any other nucleotide position in the nucleotide sequence I. In some embodiments, the base difference between the nucleotide sequence I and the nucleotide sequence set forth in SEQ ID NO: 5 can include a difference at the Z'5 position and / or a difference at a nucleotide position adjacent to Z'5. In some embodiments, the base difference between the nucleotide sequence I and the nucleotide sequence set forth in SEQ ID NO: 5 is a difference at the Z'5 position, and preferably Z'5 is an inverted abasic deoxynucleotide. In some embodiments, the difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 6 includes a difference at the Z'6 position, and Z'6 is selected from C, U or G. In some embodiments, the difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 6 is a difference at the Z'6 position, and Z'6 is selected from C, U or G. In some embodiments, the nucleotides at positions 2-19 of the nucleotide sequence II are fully reverse-complementary to the CFB mRNA in the 5' to 3' direction. In some embodiments, the nucleotide sequence II is fully reverse-complementary to the nucleotide sequence I. In some embodiments, there is a base mismatch between the 2nd nucleotide in the nucleotide sequence II in the 5' to 3' direction and the 2nd nucleotide in the nucleotide sequence I in the 3' to 5' direction. By including this base mismatch, one can have higher CFB mRNA inhibitory activity while maintaining low off-target effects. In some embodiments, the sense strand further comprises a nucleotide sequence III, the antisense strand further comprises a nucleotide sequence IV, the nucleotide sequence III has a length of 1, 2, 3, or 4 nucleotides, the nucleotide sequence IV and the nucleotide sequence III have the same length, and the nucleotide sequence IV and the nucleotide sequence III are substantially reverse-complementary or fully reverse-complementary, and the nucleotide sequence III is linked to the 5' end of the nucleotide sequence I. In some embodiments, the nucleotide sequence III and the nucleotide sequence IV each have a length of 1 nucleotide in the 5' to 3' direction, the nucleotide sequence III has a base of C, and the nucleotide sequence IV has a base of G; in this case, the length ratio of the sense strand and the antisense strand is 20 / 20; or the nucleotide sequence III and the nucleotide sequence IV each have a length of 2 nucleotides, the nucleotide sequence III has a base composition of CC in the 5' end to 3' end direction, and the nucleotide sequence IV has a base composition of GG in the 5' end to 3' end direction; in this case, the length ratio of the sense strand and the antisense strand is 21 / 21; or the nucleotide sequence III and the nucleotide sequence IV each have a length of 3 nucleotides, the nucleotide sequence III has a base composition of UCC in the 5' end to 3' end direction, and the nucleotide sequence IV has a base composition of GGA in the 5' end to 3' end direction; in this case, the length ratio of the sense strand and the antisense strand is 22 / 22; or the nucleotide sequence III and the nucleotide sequence IV each have a length of 4 nucleotides, the nucleotide sequence III has a base composition of CUCC in the 5' end to 3' end direction, and the nucleotide sequence IV has a base composition of GGAG in the 5' end to 3' end direction; in this case, the length ratio of the sense strand and the antisense strand is 23 / 23. In some embodiments, the nucleotide sequence III and the nucleotide sequence IV each have a length of 2 nucleotides, the nucleotide sequence III has a base composition of CC in the 5' end to 3' end direction, and the nucleotide sequence IV has a base composition of GG in the 5' end to 3' end direction; in this case, the length ratio of the sense strand and the antisense strand is 21 / 21. In some embodiments, the antisense strand further comprises a nucleotide sequence V, each nucleotide of the nucleotide sequence V is independently a non-fluoro-modified nucleotide, the nucleotide sequence V has a length of 1 to 3 nucleotides, is linked to the 3' end of the nucleotide sequence IV or the nucleotide sequence II, and forms a 3' overhang end of the antisense strand after forming the double-stranded oligonucleotide. In some embodiments, the nucleotide sequence V has a length of 2 nucleotides, and in the direction from the 5' end to the 3' end, the nucleotide sequence V is 2 consecutive thymine deoxynucleotides, 2 consecutive uracil nucleotides, or fully reverse complementary to the CFB mRNA. In some embodiments, the nucleotide sequence V is linked to the 3' end of the nucleotide sequence II, and in the direction from the 5' end to the 3' end, the base composition of the nucleotide sequence V is selected from GG or UU. In some embodiments, the sense strand only comprises the nucleotide sequence I, the antisense strand only comprises the nucleotide sequence II and the nucleotide sequence V, the nucleotide sequence II consists of SEQ ID NO: 6, the nucleotide sequence I consists of SEQ ID NO: 5, the nucleotide sequence V is linked to the 3' end of the nucleotide sequence II, and in the direction from the 5' end to the 3' end, the base composition of the nucleotide sequence V is GG. A fourth double-stranded oligonucleotide In some embodiments, the present disclosure further provides a fourth double-stranded oligonucleotide. The fourth double-stranded oligonucleotide comprises a sense strand and an antisense strand, the sense strand comprises a nucleotide sequence I, the nucleotide sequence I is equal in length to the nucleotide sequence set forth in SEQ ID NO: 7 and has no more than 3 base differences, the nucleotide sequence II is equal in length to the nucleotide sequence set forth in SEQ ID NO: 8 and has no more than 3 base differences: 5'-GAUGAGAUCUCUUUCCAC Z7-3' (SEQ ID NO: 7) 5'-Z8GUGGAAAGAGAUCUCAUC-3' (SEQ ID NO: 8); wherein Z7 is U, A or inverted abasic deoxynucleotide, Z8 is A or U, the nucleotide sequence I comprises a nucleotide Z'7 at a position corresponding to Z7, the nucleotide sequence II comprises a nucleotide Z'8 at a position corresponding to Z8, and Z'8 is the first nucleotide at the 5' end of the single-stranded oligonucleotide sequence. In some embodiments, the sense strand only comprises the nucleotide sequence I, and the antisense strand only comprises the nucleotide sequence II. In some embodiments, there is no more than 1 base difference between the nucleotide sequence I and the nucleotide sequence set forth in SEQ ID NO: 7, and / or no more than 1 base difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 8. In some embodiments, the base difference between the nucleotide sequence I and the nucleotide sequence set forth in SEQ ID NO: 7 can include a difference at position Z'5 and / or a base difference at any other nucleotide position in the nucleotide sequence I. In some embodiments, the base difference between the nucleotide sequence I and the nucleotide sequence set forth in SEQ ID NO: 7 can include a base difference at position Z'7 and / or at a nucleotide position adjacent to Z'7. In some embodiments, the base difference between the nucleotide sequence I and the nucleotide sequence set forth in SEQ ID NO: 7 is a base difference at position Z'7, preferably, Z'7 is an inverted abasic deoxynucleotide. In some embodiments, the difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 8 includes a difference at position Z'8, and Z'8 is selected from C, U or G. In some embodiments, the difference between the nucleotide sequence II and the nucleotide sequence set forth in SEQ ID NO: 8 is a difference at position Z'8, and Z'8 is selected from C, U or G. In some embodiments, the nucleotide at position 2-19 of the nucleotide sequence II is fully reverse-complementary to the CFB mRNA in the 5' end to 3' end direction. In some embodiments, the nucleotide sequence II is fully reverse-complementary to the nucleotide sequence I. In some embodiments, there is a base mismatch between the 2nd nucleotide in the nucleotide sequence II in the 5' end to 3' end direction and the 2nd nucleotide in the nucleotide sequence I in the 3' end to 5' end direction. By including the base mismatch, one can have a higher CFB mRNA inhibitory activity while maintaining a low off-target effect. In some embodiments, the sense strand further comprises a nucleotide sequence III, the antisense strand further comprises a nucleotide sequence IV, the nucleotide sequence III has a length of 1, 2, 3 or 4 nucleotides, the nucleotide sequence IV and the nucleotide sequence III have an equal length, and the nucleotide sequence IV and the nucleotide sequence III are substantially reverse-complementary or fully reverse-complementary, and the nucleotide sequence III is linked to the 5' end of the nucleotide sequence I. In some embodiments, the length of the nucleotide sequence III and the nucleotide sequence IV is 1 nucleotide, the base of the nucleotide sequence III is U, and the base of the nucleotide sequence IV is A, in the 5' to 3' direction; in this case, the length ratio of the sense strand to the antisense strand is 20 / 20; or the length of the nucleotide sequence III and IV is 2 nucleotides, the base composition of the nucleotide sequence III is GU, and the base composition of the nucleotide sequence IV is AC, in the 5' end to 3' end direction; in this case, the length ratio of the sense strand to the antisense strand is 21 / 21; or the length of the nucleotide sequence III and IV is 3 nucleotides, the base composition of the nucleotide sequence III is AGU, and the base composition of the nucleotide sequence IV is ACU, in the 5' end to 3' end direction; in this case, the length ratio of the sense strand to the antisense strand is 22 / 22; or the length of the nucleotide sequence III and IV is 4 nucleotides, the base composition of the nucleotide sequence III is GAGU, and the base composition of the nucleotide sequence IV is ACUC, in the 5' end to 3' end direction; in this case, the length ratio of the sense strand to the antisense strand is 23 / 23. In some embodiments, the length of the nucleotide sequence III and the nucleotide sequence IV is 2 nucleotides, the base composition of the nucleotide sequence III is GU, and the base composition of the nucleotide sequence IV is AC, in the 5' end to 3' end direction; in this case, the length ratio of the sense strand to the antisense strand is 21 / 21. In some embodiments, the antisense strand further comprises a nucleotide sequence V, each nucleotide of the nucleotide sequence V is independently a non-fluorinated modified nucleotide, the length of the nucleotide sequence V is 1 to 3 nucleotides, and the nucleotide sequence V is linked to the 3' end of the nucleotide sequence IV or the nucleotide sequence II, forming a 3' overhang end of the antisense strand after forming the double-stranded oligonucleotide. In some embodiments, the length of the nucleotide sequence V is 2 nucleotides, and the nucleotide sequence V is 2 consecutive thymine deoxynucleotides, 2 consecutive uracil nucleotides, or fully reverse complementary to the CFB mRNA, in the 5' end to 3' end direction. In some embodiments, the nucleotide sequence V is linked to the 3' end of the nucleotide sequence II, and the base composition of the nucleotide sequence V is selected from AC or UU, in the 5' end to 3' end direction. In some embodiments, the sense strand only comprises the nucleotide sequence I, the antisense strand only comprises the nucleotide sequence II and the nucleotide sequence V, the nucleotide sequence II consists of SEQ ID NO: 8, the nucleotide sequence I consists of SEQ ID NO: 7, the nucleotide sequence V is linked to the 3' end of the nucleotide sequence II, and the base composition of the nucleotide sequence V is AC, in the 5' end to 3' end direction. The fifth double-stranded oligonucleotide In some embodiments, this disclosure provides a fifth double-stranded oligonucleotide. This fifth double-stranded oligonucleotide contains a sense strand and an antisense strand, wherein the sense strand contains nucleotide sequence I, which is of the same length as the nucleotide sequence shown in SEQ ID NO:73 and differs by no more than 3 bases, and nucleotide sequence II is of the same length as the nucleotide sequence shown in SEQ ID NO:74 and differs by no more than 3 bases. 5'-GGAAGGAGGUACAUCZ93'(SEQ ID NO:73) 5'-Z 10 UGAUGUAGACCUCCUUCC-3' (SEQ ID NO:74); Where Z9 is U, A or ia, Z 10 For A or U, nucleotide sequence I contains nucleotide Z'9 at position Z9, and nucleotide sequence II contains nucleotide Z at position Z. 10 nucleotide Z' 10 The Z' 10 It is the first nucleotide at the 5' end of the single-stranded oligonucleotide sequence. In some embodiments, the sense strand contains only nucleotide sequence I, and the antisense strand contains only nucleotide sequence II. In some embodiments, the nucleotide sequence I differs from the nucleotide sequence shown in SEQ ID NO:73 by no more than one base, and / or the nucleotide sequence II differs from the nucleotide sequence shown in SEQ ID NO:74 by no more than one base. The base difference between nucleotide sequence I and the nucleotide sequence shown in SEQ ID NO:73 may include a difference at the Z'9 position and / or a base difference at any other nucleotide position in nucleotide sequence I. In some embodiments, the base difference between nucleotide sequence I and the nucleotide sequence shown in SEQ ID NO:73 may include a base difference at the Z'9 position and / or a base difference at a nucleotide position adjacent to Z'9. In some embodiments, the base difference between nucleotide sequence I and the nucleotide sequence shown in SEQ ID NO:73 is a base difference at the Z'9 position; preferably, Z'9 is a reverse debased deoxynucleotide. In some embodiments, the difference between the nucleotide sequence II and the nucleotide sequence shown in SEQ ID NO:74 includes Z' 10 The difference in position, and Z' 10 Selected from C, A, or G. In some embodiments, the difference between the nucleotide sequence II and the nucleotide sequence shown in SEQ ID NO:74 is Z'. 10the difference in position, and Z' is selected from C, A, or G. 10 selected from C, A, or G. In some embodiments, the nucleotide at position 2-19 of the nucleotide sequence II is fully reverse-complemented to the CFB mRNA in the direction from 5' end to 3' end. In some embodiments, the nucleotide sequence II is fully reverse-complemented to the nucleotide sequence I. In some embodiments, there is a base mismatch between the 2nd nucleotide in the nucleotide sequence II in the direction from 5' end to 3' end and the 2nd nucleotide in the nucleotide sequence I in the direction from 3' end to 5' end. By including this base mismatch, one can have higher CFB mRNA inhibitory activity while maintaining low off-target effects. In some embodiments, the sense strand further comprises a nucleotide sequence III, the antisense strand further comprises a nucleotide sequence IV, the nucleotide sequence III has a length of 1, 2, 3, or 4 nucleotides, the nucleotide sequence IV and the nucleotide sequence III have the same length, and the nucleotide sequence IV and the nucleotide sequence III are substantially reverse-complemented or fully reverse-complemented, and the nucleotide sequence III is linked to the 5' end of the nucleotide sequence I. In some embodiments, the nucleotide sequence III and the nucleotide sequence IV each have a length of 1 nucleotide in the direction from 5' to 3', the nucleotide sequence III has a base of C, and the nucleotide sequence IV has a base of G; in this case, the length ratio of the sense strand and the antisense strand is 20 / 20; or the nucleotide sequence III and the nucleotide sequence IV each have a length of 2 nucleotides, the nucleotide sequence III has a base composition of UC in the direction from 5' end to 3' end, and the nucleotide sequence IV has a base composition of GA; in this case, the length ratio of the sense strand and the antisense strand is 21 / 21; or the nucleotide sequence III and the nucleotide sequence IV each have a length of 3 nucleotides, the nucleotide sequence III has a base composition of CUC in the direction from 5' end to 3' end, and the nucleotide sequence IV has a base composition of GAG; in this case, the length ratio of the sense strand and the antisense strand is 22 / 22; or the nucleotide sequence III and the nucleotide sequence IV each have a length of 4 nucleotides, the nucleotide sequence III has a base composition of ACUC in the direction from 5' end to 3' end, and the nucleotide sequence IV has a base composition of GAGU; in this case, the length ratio of the sense strand and the antisense strand is 23 / 23. In some embodiments, the nucleotide sequence III and the nucleotide sequence IV each have a length of 2 nucleotides, the nucleotide sequence III has a base composition of UC in the direction from 5' end to 3' end, and the nucleotide sequence IV has a base composition of GA; in this case, the length ratio of the sense strand and the antisense strand is 21 / 21. In some embodiments, the antisense strand further comprises a nucleotide sequence V, each nucleotide of the nucleotide sequence V is independently a non-fluoro-modified nucleotide, the nucleotide sequence V has a length of 1 to 3 nucleotides, is linked to the 3' end of the nucleotide sequence IV or the nucleotide sequence II, and forms a 3' overhang end of the antisense strand after the formation of the double-stranded oligonucleotide. In some embodiments, the nucleotide sequence V has a length of 2 nucleotides, and in the direction from the 5' end to the 3' end, the nucleotide sequence V is 2 consecutive thymine deoxynucleotides, 2 consecutive uracil nucleotides, or fully reverse complementary to the CFB mRNA. In some embodiments, the nucleotide sequence V is linked to the 3' end of the nucleotide sequence II, and in the direction from the 5' end to the 3' end, the base composition of the nucleotide sequence V is selected from GA or UU. In some embodiments, the sense strand comprises only the nucleotide sequence I, the antisense strand comprises only the nucleotide sequence II and the nucleotide sequence V, the nucleotide sequence II consists of SEQ ID NO: 74, the nucleotide sequence I consists of SEQ ID NO: 73, the nucleotide sequence V is linked to the 3' end of the nucleotide sequence II, and in the direction from the 5' end to the 3' end, the base composition of the nucleotide sequence V is GA. The sixth double-stranded oligonucleotide In some embodiments, the present disclosure further provides a sixth double-stranded oligonucleotide. The sixth double-stranded oligonucleotide comprises a sense strand and an antisense strand, the sense strand comprises a nucleotide sequence I, the nucleotide sequence I is equal in length to and differs by no more than 3 bases from the nucleotide sequence set forth in SEQ ID NO: 75, the nucleotide sequence II is equal in length to and differs by no more than 3 bases from the nucleotide sequence set forth in SEQ ID NO: 76: 5'-CCCGAGACUUUCACAUCAZ 11 -3' (SEQ ID NO: 75) 5'-Z 12 UGAUGUGAAAGUCUCGGG-3' (SEQ ID NO: 76); wherein Z 11 is U, A or ia, Z 12 is A or U, the nucleotide sequence I comprises a nucleotide Z' 11 corresponding to the position of Z 11 , the nucleotide sequence II comprises a nucleotide Z' 12 corresponding to the position of Z 12 , and Z' 12 is the first nucleotide at the 5' end of the single-stranded oligonucleotide sequence. In some embodiments, the sense strand comprises only the nucleotide sequence I, and the antisense strand comprises only the nucleotide sequence II. In some embodiments, the nucleotide sequence I has no more than 1 base difference between the nucleotide sequence set forth in SEQ ID NO: 75, and / or the nucleotide sequence II has no more than 1 base difference between the nucleotide sequence set forth in SEQ ID NO: 76. In some embodiments, the nucleotide sequence I has a base difference at position Z' between the nucleotide sequence set forth in SEQ ID NO: 75, and / or the nucleotide sequence II has a base difference at position Z' between the nucleotide sequence set forth in SEQ ID NO: 76. 11 In some embodiments, the nucleotide sequence I has a base difference at position Z' between the nucleotide sequence set forth in SEQ ID NO: 75, and / or the nucleotide sequence II has a base difference at position Z' between the nucleotide sequence set forth in SEQ ID NO: 76. 11 In some embodiments, the nucleotide sequence I has a base difference at position Z' between the nucleotide sequence set forth in SEQ ID NO: 75, and / or the nucleotide sequence II has a base difference at position Z' between the nucleotide sequence set forth in SEQ ID NO: 76. 11 In some embodiments, the nucleotide sequence I has a base difference at position Z' between the nucleotide sequence set forth in SEQ ID NO: 75, and / or the nucleotide sequence II has a base difference at position Z' between the nucleotide sequence set forth in SEQ ID NO: 76. 11 In some embodiments, the nucleotide sequence I has a base difference at position Z' between the nucleotide sequence set forth in SEQ ID NO: 75, and / or the nucleotide sequence II has a base difference at position Z' between the nucleotide sequence set forth in SEQ ID NO: 76. 11 In some embodiments, the base difference at position Z' is a reverse dealkylated deoxynucleotide. In some embodiments, the nucleotide sequence II has a difference at position Z' between the nucleotide sequence set forth in SEQ ID NO: 76, and Z' is selected from C, A, or G. 12 In some embodiments, the nucleotide sequence II has a difference at position Z' between the nucleotide sequence set forth in SEQ ID NO: 76, and Z' is selected from C, A, or G. 12 In some embodiments, the nucleotide sequence II has a difference at position Z' between the nucleotide sequence set forth in SEQ ID NO: 76, and Z' is selected from C, A, or G. 12 In some embodiments, the nucleotide sequence II has a difference at position Z' between the nucleotide sequence set forth in SEQ ID NO: 76, and Z' is selected from C, A, or G. 12 In some embodiments, the nucleotide sequence II has a difference at position Z' between the nucleotide sequence set forth in SEQ ID NO: 76, and Z' is selected from C, A, or G. In some embodiments, the 2nd-19th nucleotides of the nucleotide sequence II are fully reverse-complementary to the CFB mRNA in the 5' end to 3' end direction. In some embodiments, the nucleotide sequence II is fully reverse-complementary to the nucleotide sequence I. In some embodiments, the 2nd nucleotide in the nucleotide sequence II in the 5' end to 3' end direction has a base mismatch with the 2nd nucleotide in the nucleotide sequence I in the 3' end to 5' end direction. By including this base mismatch, one can have higher CFB mRNA inhibitory activity while maintaining low off-target effects. In some embodiments, the sense strand further comprises a nucleotide sequence III, the anti-sense strand further comprises a nucleotide sequence IV, the nucleotide sequence III has a length of 1, 2, 3, or 4 nucleotides, the nucleotide sequence IV and the nucleotide sequence III have equal length, and the nucleotide sequence IV and the nucleotide sequence III are substantially reverse complementary or completely reverse complementary, and the nucleotide sequence III is linked to the 5' end of the nucleotide sequence I. In some embodiments, the nucleotide sequence III and the nucleotide sequence IV each has a length of 1 nucleotide, the nucleotide sequence III has a base of G, and the nucleotide sequence IV has a base of C, in the 5' to 3' direction; or the nucleotide sequence III and the nucleotide sequence IV each has a length of 2 nucleotides, the nucleotide sequence III has a base composition of CG, and the nucleotide sequence IV has a base composition of CG, in the 5' end to 3' end direction; or the nucleotide sequence III and the nucleotide sequence IV each has a length of 3 nucleotides, the nucleotide sequence III has a base composition of ACG, and the nucleotide sequence IV has a base composition of CGU, in the 5' end to 3' end direction; or the nucleotide sequence III and the nucleotide sequence IV each has a length of 4 nucleotides, the nucleotide sequence III has a base composition of CACG, and the nucleotide sequence IV has a base composition of CGUG, in the 5' end to 3' end direction. In some embodiments, the nucleotide sequence III and the nucleotide sequence IV each has a length of 2 nucleotides, the nucleotide sequence III has a base composition of CG, and the nucleotide sequence IV has a base composition of CG, in the 5' end to 3' end direction. In some embodiments, the anti-sense strand further comprises a nucleotide sequence V, each nucleotide of the nucleotide sequence V is independently a non-fluorinated modified nucleotide, the nucleotide sequence V has a length of 1 to 3 nucleotides, and is linked to the 3' end of the nucleotide sequence IV or the nucleotide sequence II, and forms a 3' overhang end of the anti-sense strand after forming the double-stranded oligonucleotide. In some embodiments, the nucleotide sequence V has a length of 2 nucleotides, and is 2 consecutive thymine deoxynucleotides, 2 consecutive uracil nucleotides, or completely reverse complementary to the CFB mRNA, in the 5' end to 3' end direction. In some embodiments, the nucleotide sequence V is linked to the 3' end of the nucleotide sequence II, and the base composition of the nucleotide sequence V is selected from CG or UU, in the 5' end to 3' end direction. In some embodiments, the sense strand comprises only the nucleotide sequence I, the antisense strand comprises only the nucleotide sequence II and the nucleotide sequence V, the nucleotide sequence II consists of SEQ ID NO: 76, the nucleotide sequence I consists of SEQ ID NO: 75, the nucleotide sequence V is linked at the 3' end of the nucleotide sequence II, and the base composition of the nucleotide sequence V, in the 5' end to 3' end direction, is CG. In some embodiments, the double-stranded oligonucleotide is one of siRNAa1, siRNAb1, siRNAc1, siRNAd1, siRNAe1, or siRNAf1 as shown in Table 1 below: Table 1 siRNA sequences of the disclosure wherein capital letters C, G, U, A, and T represent the base composition of a nucleotide; lower case letter o represents that the nucleotide represented by the capital letter adjacent to the left of the letter o is an alkoxy-modified nucleotide; lower case letter f represents that the nucleotide represented by the capital letter adjacent to the left of the letter f is a fluoro-modified nucleotide; each N is independently U or T; lower case letter s represents that the two nucleotides represented by the two capital letters adjacent to the left and right of the letter s are connected by a phosphorothioate group; lower case letter d represents that the nucleotide represented by the capital letter adjacent to the right of the letter d is a deoxyribonucleotide; and ia represents an inverted abasic deoxyribonucleotide. In some embodiments, each alkoxy-modified nucleotide is a 2'-methoxy-modified nucleotide. The single-stranded oligonucleotides and / or double-stranded oligonucleotides provided by the disclosure can be obtained by conventional oligonucleotide preparation methods in the art, such as solid-phase synthesis and liquid-phase synthesis methods. Among them, solid-phase synthesis has been commercialized as a subscription service. Methods for preparing nucleoside monomers with corresponding modifications and methods for introducing modified nucleotide groups into single-stranded oligonucleotides and / or double-stranded oligonucleotides described by the disclosure can be used to introduce modified nucleotide groups into single-stranded oligonucleotides and / or double-stranded oligonucleotides by using nucleoside monomers with corresponding modifications, which are well known to those skilled in the art. All modified nucleoside monomers can be commercially available or prepared by known methods. The single-stranded oligonucleotide, the double-stranded oligonucleotide provided by the present disclosure can be used alone, or form a pharmaceutical composition with a pharmaceutically acceptable carrier, or form an oligonucleotide conjugate with a delivery group, or in any other suitable form. An effective amount of the single-stranded oligonucleotide, the double-stranded oligonucleotide, the pharmaceutical composition or the oligonucleotide conjugate is contacted with a cell to modulate the expression of a target gene, or an effective amount of the single-stranded oligonucleotide, the double-stranded oligonucleotide, the oligonucleotide conjugate or the pharmaceutical composition is administered to a subject to modulate the expression of a target gene, to achieve the purpose of treating a pathological condition or a disease associated with the expression level of the target gene. Oligonucleotide conjugate In another aspect, the present disclosure provides an oligonucleotide conjugate containing an oligonucleotide group and a delivery group conjugated to the oligonucleotide group, the oligonucleotide group is independently a group formed by removing one or more atoms or atom groups from the single-stranded oligonucleotide or the double-stranded oligonucleotide provided by the present disclosure. In the context of the present disclosure, unless otherwise specified, "conjugation" refers to the connection between two or more chemical moieties each having a specific function in a manner of covalent connection; accordingly, "conjugate" refers to a compound formed by the covalent connection between the respective chemical moieties. Further, "oligonucleotide conjugate" means a compound formed by the covalent connection of one or more chemical moieties having a specific function to an oligonucleotide. Oligonucleotide conjugate should be understood as a general term for a plurality of oligonucleotide conjugates or an oligonucleotide conjugate represented by a certain chemical formula, depending on the context. In the context of the present disclosure, "conjugation molecule" should be understood as a specific compound that can be conjugated to an oligonucleotide by a reaction to ultimately form an oligonucleotide conjugate of the present disclosure. The delivery group is a group for delivering the single-stranded oligonucleotide group or the double-stranded oligonucleotide group into a cell expressing CFB mRNA. In some embodiments, the delivery group comprises a linker group and a pharmaceutically acceptable targeting group, and the single-stranded oligonucleotide group or the double-stranded oligonucleotide group, the linker group and the targeting group are covalently or non-covalently connected in sequence, each of the targeting groups is selected from a ligand capable of binding to a cell surface receptor or a group capable of increasing compatibility with a tissue. In some embodiments, each of the targeting groups independently targets the liver. In some embodiments, the targeting group is 1-6. In one embodiment, the targeting group is 2-4. The double-stranded oligonucleotide group can be conjugated to the delivery group non-covalently or covalently, for example, can be covalently conjugated to the delivery group. In some embodiments, the oligonucleotide group is a double-stranded oligonucleotide group, the conjugation site of which to the delivery group can be at the 3' end or 5' end of the sense strand of the double-stranded oligonucleotide, or at the 5' end of the antisense strand, or in the internal sequence of the double-stranded oligonucleotide. In some embodiments, the conjugation site of the double-stranded oligonucleotide group to the delivery group is at the 3' end of the sense strand of the double-stranded oligonucleotide. In some embodiments, the delivery group can be linked at any position of the nucleotide, such as the phosphate group, the 2'-, 3'- or 5'-position hydroxyl of the ribose, or the base. When the delivery group is linked at the 3'- or 5'-end of the single-stranded oligonucleotide or the sense strand of the double-stranded oligonucleotide, the delivery group is usually linked to the oxygen atom formed after the removal of the hydrogen atom from the 3'- or 5'-hydroxyl of the nucleotide; when the delivery group is linked in the internal sequence of the single-stranded oligonucleotide or the double-stranded oligonucleotide, the delivery group is usually linked to the phosphate group, the ribose ring or the base. In some embodiments, the delivery group can be linked to the 3'-position hydroxyl of the nucleotide in the internal sequence of the single-stranded oligonucleotide or the double-stranded oligonucleotide, in which case the nucleotides are connected by 2'-5' phosphodiester bonds. Various connection modes can be referred to the description in the following non-patent literature: Muthiah Manoharan et. al. siRNA conjugates carrying sequentially assembled trivalent N-acetylgalactosamine linked through nucleosides elicit robust gene silencing in vivo in hepatocytes. ACS Chemical biology, 2015, 10(5): 1181-7. The disclosure thereof is incorporated herein by reference in its entirety. In some embodiments, the oligonucleotide and the delivery group can be connected by acid-labile or reducible chemical bonds, which can be degraded in the acidic environment of the intracellular endosome, thereby converting the double-stranded oligonucleotide group into a free double-stranded oligonucleotide. For non-degradable conjugation, the delivery group can be linked to the sense strand of the single-stranded oligonucleotide or the double-stranded oligonucleotide group, so as to minimize the impact of conjugation on the activity of the double-stranded oligonucleotide group. The targeting groups can be attached to the double stranded oligonucleotide group via a suitable linker group, which can be selected by one of skill in the art depending on the specific type of targeting group. For example, when the targeting group is a group that targets a receptor on the surface of a hepatocyte cell, such linker groups, types of targeting groups, and ways of attaching to a double stranded oligonucleotide can be found in the disclosure of WO2015006740A2, the disclosure of which is incorporated herein by reference in its entirety. In some embodiments, the targeting group can be a ligand group that is routinely used in the art of oligonucleotide drug delivery, such as the various ligand groups described in WO2009082607A2, the disclosure of which is incorporated herein by reference in its entirety. In some embodiments, at least one or each of the targeting groups is selected from a ligand group that is capable of binding to a receptor on the surface of a cell that expresses CFB mRNA. In some embodiments, at least one or each of the targeting groups is selected from a small molecule ligand group that has affinity for an asialoglycoprotein receptor on the surface of a hepatocyte cell. In some embodiments, at least one or each of the targeting groups is selected from a ligand group capable of binding to a surface receptor of a mammalian liver parenchymal cell. In some embodiments, each of the targeting groups is independently a ligand having affinity for an asialoglycoprotein receptor on the surface of a mammalian liver cell. In some embodiments, each of the targeting groups is independently an asialoglycoprotein or sugar. In some embodiments, each of the targeting groups is independently selected from one of the group consisting of D-mannopyranose, L-mannopyranose, D-arabinose, D-xylofuranose, L-xylofuranose, D-glucose, L-glucose, D-galactose, L-galactose, a-D-mannofuranose, β-D-mannofuranose, a-D-mannopyranose, β-D-mannopyranose, a-D-glucopyranose, β-D-glucopyranose, a-D-glucoruranose, β-D-glucoruranose, a-D-fructofuranose, a-D-fructopyranose, a-D-galactopyranose, β-D-galactopyranose, a-D-galactofuranose, β-D-galactofuranose, glucosamine, sialic acid, galactosamine, N-acetylgalactosamine, N-trifluoroacetylgalactosamine, N-propionylgalactosamine, N-n-butyrylgalactosamine, N-isobutyrylgalactosamine, 2-amino-3-0-[(R)-1-carboxyethyl]-2-deoxy-β-D-glucopyranose, 2-deoxy-2-methylamino-L- pyranoglucose, 4,6-dideoxy-4-formamido-2,3-di-0-methyl-D-mannopyranose, 2-deoxy-2- sulfonamido-D-glucopyranose, N-glycolyl-a-neuraminic acid, 5-thio-β-D-glucopyranose, 2,3,4-tri-0-acetyl-1-thio-6-0-trityl-a-D-glucopyranoside methyl ester, 4-thio-β-D- galactopyranose, 3,4,6,7-tetra-0-acetyl-2-deoxy-1,5-dithio-a-D-glucopyranoside ethyl ester, 2,5- anhydro-D-allosonitrile, ribose, D-ribose, D-4-thioribose, L-ribose, L-4-thioribose, and a group formed by removing one atom or group from one of the foregoing. In some embodiments, at least one or each of the targeting groups is a galactosyl group or an N-acetylgalactosamine group. In some embodiments, the double-stranded oligonucleotide group is capable of modulating the expression level of CFB mRNA in a liver parenchymal cell. The delivery group in the oligonucleotide conjugates of the present disclosure can be various delivery groups known to those skilled in the art of oligonucleotide drugs. In some embodiments, the linking group in the oligonucleotide conjugates of the present disclosure has a structure as shown in formula (301): wherein k is an integer from 1 to 5, denotes the site of covalent attachment of the groups; all L A attached to L CThe same atom in; or, each L A Independently connected to L C Different atoms in it. In some implementations, L C It has -NH-C(H) n301 (CH2O-) k The structure shown is such that k is an integer from 1 to 3, and n301 = 3 - k; L B The length is 5-20 atoms. In some implementations, each L A Independently, it is a straight-chain alkylene group with a length of 5-20 carbon atoms, wherein one or more methylene groups are optionally replaced by any one or more groups selected from the group consisting of: C(O), NH, O, S, 1,2,3-triazolyl, butadieneyl. In some implementations, L A Having a structure containing amide bonds as shown in formula (302), L B It has a structure as shown in equation (303): Where, n 302 q 302 and p 302 Each is an independent integer from 2 to 6; optionally, n 302 q 302 and p 302 Each is independently 2 or 3; n 303 n is an integer between 4 and 16, optionally n 303 For integers between 8 and 12, This indicates the site where the group is covalently linked. In some embodiments, the linking group has a structure as shown in formula (304) or formula (305): In the linking group, each L A Each of the target groups is connected via an ether bond and via L C The oxygen atom of the hydroxyl group in some of the middle groups is related to L. C Partially linked by ether bonds; L B Through the carbonyl group in formula (303) and L C The nitrogen atom of the amino group in some of them forms an amide bond and is connected to the double-stranded oligonucleotide group through the oxygen atom in formula (303) by forming a phosphate ester bond or a thiophosphate ester bond. In some embodiments, the oligonucleotide conjugates provided in this disclosure have a structure as shown in formula (305): Nu represents a double-stranded oligonucleotide group formed by the single-stranded oligonucleotide or the double-stranded oligonucleotide provided by the present disclosure. In some embodiments, the linking group in the oligonucleotide conjugate of the present disclosure has a structure represented by formula (306): wherein n 306 is an integer from 0 to 3, each p 306 is independently an integer from 1 to 6, represents the site of covalent attachment of groups; the linking group is connected to the targeting group via an ether bond through the oxygen atom marked by *; the linking group is connected to the double-stranded oligonucleotide via at least one of the oxygen atoms marked by # to form a phosphonate bond or a phosphorothioate bond, and the rest of the oxygen atoms marked by # are connected to hydrogen atoms to form hydroxyl groups or to C1-C3 alkyl groups to form C1-C3 alkoxy groups; In some embodiments, the oligonucleotide conjugate of the present disclosure has a structure represented by formula (307): wherein Nu represents a double-stranded oligonucleotide group formed by the single-stranded oligonucleotide or the double-stranded oligonucleotide provided by the present disclosure. In some embodiments, the oligonucleotide conjugate of the present disclosure has a structure represented by formula (308): wherein n 308 is an integer selected from 2 to 4; each m 308 is independently an integer selected from 2 to 5; each R 308 is independently a hydrogen atom, a methyl group or an ethyl group, or 2 R 308 on the same carbon atom together form a carbonyl group; one of the groups represented by A0, respectively, is an oligonucleotide group, which is a group formed by removing one atom or group of atoms from the single-stranded oligonucleotide or the double-stranded oligonucleotide described in the present disclosure; all the remaining A0are targeting groups, each of which is the same or different, and the definition and selection range thereof are as described above. In some embodiments, each targeting group is independently selected from one of the ligands having affinity to the asialoglycoprotein receptor on the surface of mammalian liver parenchymal cells. each L1is independently a divalent linking group having a length of 1-70 or 3-25 atoms; represents the site of covalent attachment of groups. In some embodiments, each L1is independently a straight-chain alkylene of 1-70 or 1-20 carbon atoms, wherein one or more carbon atoms are optionally replaced by any one or more from the group consisting of C(O), NH, O, S, CH=N, S(O)2, OP(O)2, OP(O)(S), C2-C 10 alkenylene, C2-C 10 alkynylene, C6-C 10 arylene, C3-C 18 heterocyclylene, and C5-C 10 heteroarylene; and the straight-chain alkylene can optionally have substituents of any one or more from the group consisting of C1-C 10 alkyl, C6-C 10 aryl, C5-C 10 heteroaryl, C1-C 10 haloalkyl, -OC1-C 10 alkyl, OC1-C 10 alkylphenyl, -C1-C 10 alkyl-OH, -OC1-C 10 haloalkyl, -SC1-C 10 alkyl, -SC1-C 10 alkylphenyl, -C1-C 10 alkyl-SH, -SC1-C 10 haloalkyl, halogen substituent, -OH, -SH, -NH2, -C1-C 10 alkyl-NH2, -N(C1-C 10 alkyl)(C1-C 10 alkyl), -NH(C1-C 10 alkyl), N(C1-C 10 alkyl)(C1-C 10 alkylphenyl), NH(C1-C 10 alkylphenyl), cyano, nitro, -CO2H, -C(O)O(C1-C 10 alkyl), -CON(C1-C 10 alkyl)(C1-C 10 alkyl), -CONH(C1-C 10 alkyl), -CONH2, -NHC(O)(C1-C 10 alkyl), -NHC(O)(phenyl), -N(C1-C 10 alkyl)C(O)(C1-C 10 alkyl), -N(C1-C 10 alkyl)C(O)(phenyl), C(O)C1-C 10 alkyl, C(O)C1-C10 alkylphenyl, C(O)C1-C 10 haloalkyl, -OC(O)C1-C 10 alkyl, -SO2(C1-C 10 alkyl), -SO2(phenyl), -SO2(C1-C 10 haloalkyl), -SO2NH2, -SO2NH(C1-C 10 alkyl), -SO2NH(phenyl), -NHSO2(C1-C 10 alkyl), -NHSO2(phenyl), and -NHSO2(C1-C 10 haloalkyl). It will be understood by the skilled person that, although for convenience L1is defined as being a linker group formed from a linear alkylene group by substitution or replacement, it can not be a linear group or an amine or alkenyl group as a result of the above-mentioned substitution and / or replacement. Unless otherwise stated, the "length" of any group in the chemical structures depicted in the present disclosure refers to the number of atoms in the longest chain of atoms in the group, not counting hydrogen atoms; where there are multiple ways of connecting two atoms (for example, two atoms belong to the same cyclic group, so that there are at least 2 chains of atoms that include the two atoms), the length is calculated as the shortest chain of atoms between the two atoms. For example, 1,4-cyclohexanediyl, 1,4-piperidinediyl, 1,4- phenylenyl, 1,4-piperazinediyl are each calculated as 4 atoms in length, whereas 1,2- cyclopentanediyl is calculated as only 2 atoms in length. The role of L1covalently linked to A0representing a double-stranded oligonucleotide group is to allow covalent linkage of the oligonucleotide group to the targeting group, to allow entry of the oligonucleotide conjugate comprising the oligonucleotide group into a cell expressing CFB mRNA via the targeting action of the targeting group, and not to affect the CFB mRNA level modulating action of the double-stranded oligonucleotide group once it has entered a cell expressing CFB mRNA. Thus, in some embodiments, L1covalently linked to A0representing an oligonucleotide group has a length of 3-20 atoms, or 4-15 atoms, or 5-12 atoms. In some embodiments, L1covalently linked to A0representing an oligonucleotide group is selected from one or more of the following combinations of A1, A2, A4, A5, A10, A16, A18, and A19with a phosphate group or a modified phosphate group: wherein j1is an integer from 2 to 10; denotes the site of covalent linkage of the groups. In some embodiments, R2is selected from the combination of linkage of at least two of A1, A2, A4, A10, and A16to a phosphate group or a modified phosphate group; in some embodiments, R2is selected from the combination of linkage of at least two of A1, A2, A10to a phosphate group or a modified phosphate group. In some embodiments, L1covalently linked to A0representing an oligonucleotide group has a structure as shown in formula (B1), (B2), (B3), or (B4): wherein, represents the site of covalent linkage of the groups, L B1 and L B2 are the same or different, independently selected from one of the following groups or any combination of linkage: -(CH2) q1 -, -CH(OH)-, -CH(CH2OH)-, -NH-, -O-, -S-, 1,4-cyclohexanediyl, 1,4-piperidinediyl, 1,4- phenylenediyl, 1,4-piperazinediyl, pyrrolidinediyl, wherein q1is an integer from 1 to 6, L B1 and L B2 each independently have a length of 1 to 20 atoms. In some embodiments, L B1 and L B2 each independently have a length of 1 to 10 atoms. In some embodiments, L B1 and L B2 each independently have a length of 1 to 6 atoms. L B3 is selected from one of a phosphate group, a thiophosphate group, a dithiophosphate group, covalently linked to the oxygen atom remaining after removal of one hydrogen atom from the ribose 5' position hydroxyl group of the 5' terminal nucleotide, or the ribose 3' position hydroxyl group of the 3' terminal nucleotide of the sense strand or the antisense strand of the double stranded oligonucleotide group. In some embodiments, L B3 is a phosphate group, covalently linked to the oxygen atom remaining after removal of one hydrogen atom from the ribose 5' position hydroxyl group of the 5' terminal nucleotide, or the ribose 3' position hydroxyl group of the 3' terminal nucleotide of the sense strand of the double stranded oligonucleotide group. In some embodiments, where the oligonucleotide conjugate of the present disclosure is prepared by a process of solid phase synthesis, L1covalently linked to A0representing a double stranded oligonucleotide group needs to contain simultaneously a linking site to N on the nitrogen-containing backbone, a linking site to the oligonucleotide group, and a functional group capable of linking to a solid support. In some embodiments, the linking site to N on the nitrogen-containing backbone in L1covalently linked to A0representing a double stranded oligonucleotide group forms an amide bond with N, the oligonucleotide group is covalently linked through a phosphodiester bond, and the functional group capable of linking to a solid support is a hydroxyl or an amino group. In some embodiments, R2is B5, B6, B5’, or B6’: wherein, represents a site of covalent linkage of groups. q2may be an integer from 1 to 10, and in some embodiments, q2is an integer from 1 to 5. The role of L1covalently linked to A0representing a targeting group is to place the targeting group in a suitable spatial position, so as to better bind to the receptor, so as to specifically target and enter the relevant cell. Therefore, L1covalently linked to A0representing a targeting group can be used in the present disclosure as long as it has a suitable length, and the chemical properties do not have a significant impact on delivery. In some embodiments, each L1covalently linked to A0representing a targeting group is independently a divalent linking group of 3-25 atoms in length. In some embodiments, each L1covalently linked to A0representing a targeting group is independently 4-15 atoms in length. In some embodiments, each L1covalently linked to A0representing a targeting group is 5-10 atoms in length. In some embodiments, each L1covalently linked to A0representing a targeting group is the same in length. In some embodiments, each L1covalently linked to A0representing a targeting group is the same or different, and is independently selected from the group consisting of the groups represented by formulae (L3)-(L18) and any linking combination thereof: wherein each j1is an integer from 2 to 10; each R’ is independently a hydrogen atom or a C1-C3 alkyl group, represents a site of covalent linkage of groups. For simplicity of synthesis and / or stability of chemical properties, in some embodiments, each L1covalently linked to A0representing a targeting group is independently a combination of at least 2 linking units, each independently having a structure represented by any one of formulae (L3)-(L7). In some embodiments, each linking unit independently has a structure represented by any one of formulae (L3), (L4), and (L7). For simplicity of synthesis, in some embodiments, each L1covalently linked to A0representing a targeting group includes a carbonyl group attached to a nitrogen atom represented in formula (308). In some embodiments, each L1covalently linked to A0representing a targeting group independently has a structure represented by formula (L20) or (L21): wherein j2is an integer from 4 to 9, and j3is 1 or 2. In some embodiments, j2is 5, 6, or 7, and j3is 1. In some embodiments, each L1covalently linked to A0representing a targeting group is the same. In the conjugate of the present disclosure, the number of targeting groups and the spacing between the targeting groups are such that a proper spatial configuration of multiple targeting groups is provided. To this end, n308and each m308are independently an integer selected from 2 to 4. In some embodiments, n308is 3 or 4, such that the number of targeting groups in the conjugate of the present disclosure is 3 or 4, which can better bind to the surface receptors of hepatocytes. In some embodiments, n308is 3, and each m308is independently 3 or 4. As understood by one skilled in the art, each R 308 is independently a hydrogen atom, a methyl group, or an ethyl group, without affecting the delivery effect of the oligonucleotide conjugate, and each can achieve the purpose of the present disclosure. In some embodiments, for simplicity of synthesis, each R 308 is a hydrogen atom. In the conjugate of the present disclosure, each targeting group is the same or different, and is independently selected from a ligand group capable of binding to a cell surface receptor. In some embodiments, at least one or each targeting group is a group capable of targeting the liver. In some embodiments, at least one or each targeting group is one of ligand groups capable of having affinity to a receptor on the surface of a mammalian hepatocyte. In some embodiments, at least one or each targeting group is one of ligand groups capable of having affinity to an asialoglycoprotein receptor (ASGPR) on the surface of a mammalian hepatocyte. In some embodiments, each targeting group is a galactose group or an N-acetylgalactosamine group formed by removing one atom or group from a galactose group or an N-acetylgalactosamine group. In some embodiments, the oligonucleotide conjugate of the present disclosure has a structure represented by Formula (403), (404), (405), (406), (407), (408), (409), (410), (411), (412), (413), (414), (415), (416), (417), (418), (419), (420), (421), or (422): wherein Nu represents an oligonucleotide group, such as a single-stranded oligonucleotide group or a double-stranded oligonucleotide group formed by a single-stranded oligonucleotide or a double-stranded oligonucleotide provided by the present disclosure. In some embodiments, the oligonucleotide group is a double-stranded oligonucleotide group, and the P atom shown in the above structural formula is covalently linked to the 3’ terminal nucleotide of the sense strand of the double-stranded oligonucleotide group. In some embodiments, the 3’ terminal nucleotide of the sense strand of the double-stranded oligonucleotide group is an inverted deoxyabasic nucleotide, and the P atom shown in the above structural formula is covalently linked to the double-stranded oligonucleotide group by replacing the hydrogen atom in the hydroxyl group of the ribose ring connected to the 3’ position of the ribose of the inverted deoxyabasic nucleotide of the 3’ terminal nucleotide of the sense strand of the double-stranded oligonucleotide group represented by Nu with a methylene group. In some embodiments, the P atom shown in Formula (403)-(422) is covalently linked to the oxygen atom remaining after removing one hydrogen atom from the 3’ position hydroxyl group of the ribose of the 3’ terminal nucleotide of the sense strand of the double-stranded oligonucleotide group represented by Nu. In some embodiments, the P atom shown in Formula (403)-(422) is covalently linked to the oxygen atom of the inverted deoxyabasic nucleotide ia shown in Formula (35) connected to the ribose ring by a methylene group at the 3’ terminal of the sense strand of the siRNA represented by Nu, thereby covalently linking to the sense strand of the siRNA. In some embodiments, the oligonucleotide group comprised in the oligonucleotide conjugate of the present disclosure can be an siRNA group formed by removing one atom or group of atoms from an siRNA, in which case the oligonucleotide conjugate of the present disclosure is also referred to as an siRNA conjugate. In some embodiments, the double-stranded oligonucleotide group comprised in the oligonucleotide conjugate of the present disclosure can be an siRNA group formed by, for example, the siRNAs listed in Table 1. The siRNA conjugates comprising these siRNA groups exhibit excellent stability and high CFB mRNA inhibition activity. In some embodiments, the oligonucleotide conjugate is one of Conjugate 1-Conjugate 44 listed in Table 2A. Preparation of the oligonucleotide conjugate of the present disclosure The oligonucleotide conjugate of the present disclosure can be prepared by various suitable methods by those skilled in the art. For example, when the nucleoside monomers are linked one by one according to the sequence and modification scheme of the single-stranded oligonucleotide or the sense strand and the antisense strand of the double-stranded oligonucleotide of the present disclosure by the solid-phase synthesis method, the delivery group can be introduced by the methods described in detail in the prior art to synthesize the oligonucleotide conjugate of the present disclosure. For example, the preparation methods of various siRNA conjugates are described in detail in WO2015006740A2. In the case of siRNA as the double-stranded oligonucleotide, the oligonucleotide conjugate of the present disclosure can also be obtained by means well known to those skilled in the art. The preparation method of the structure represented by Formula (305) is described in WO2014025805A1, and the preparation method of the structure represented by Formula (307) is described in Rajeev et al., ChemBioChem 2015, 16, 903-908. The preparation method of the oligonucleotide conjugate represented by Formula (308) is also disclosed in detail in Chinese Patent Application CN110959011A. The contents of the above documents are incorporated herein by reference in their entirety. Pharmaceutically acceptable salt In yet another aspect, the present disclosure also provides a pharmaceutically acceptable salt of the single-stranded oligonucleotide, the double-stranded oligonucleotide, or the oligonucleotide conjugate of the present disclosure. The pharmaceutically acceptable salt is known to those skilled in the art. By forming a salt form, the pharmaceutically acceptable salt of the single-stranded oligonucleotide, the double-stranded oligonucleotide, or the oligonucleotide conjugate of the present disclosure can exhibit better solubility, bioavailability, or stability than the single-stranded oligonucleotide, the double-stranded oligonucleotide, or the oligonucleotide conjugate itself. In the double-stranded oligonucleotide or the oligonucleotide conjugate of the present disclosure, each adjacent nucleotide is connected by a phosphodiester bond or a phosphorothioate bond, and the non-bridging oxygen atom or the sulfur atom in the phosphodiester bond or the phosphorothioate bond carries a negative charge, which can exist in the form of a hydroxyl group or a thiol group, and the hydrogen ion in the hydroxyl group or the thiol group can also be partially or completely replaced by a cation. The cation can be any cation, such as a metal cation, an ammonium ion NH4+ One of the organic ammonium cations. Further, there can also be a salt-forming group in the delivery group. For the purpose of improving solubility and / or improving bioavailability, in some embodiments, the pharmaceutically acceptable salt is a water-soluble salt of part or all of the double-stranded oligonucleotide or the oligonucleotide conjugate. In some embodiments, the water-soluble salt can be an amine salt, an alkali metal salt, or an alkaline earth metal salt, in some embodiments, the amine salt is selected from one or more of an ammonium salt, a methylamine salt, a tertiary amine salt, a quaternary ammonium salt, the alkali metal salt is selected from a potassium salt or a sodium salt, and the alkaline earth metal salt is selected from a calcium salt or a magnesium salt. In some embodiments, the tertiary amine salt is a triethylamine salt, a triisopropylamine salt, or a N,N-diisopropylethylamine salt. In some embodiments, the pharmaceutically acceptable salt is a salt or a partial salt of the single-stranded oligonucleotide, the double-stranded oligonucleotide, or the oligonucleotide conjugate, the salt is one or more of a methylamine salt, a triethylamine salt, or a sodium salt. In some embodiments, the pharmaceutically acceptable salt of the single-stranded oligonucleotide, the double-stranded oligonucleotide, or the oligonucleotide conjugate is a sodium salt or a partial sodium salt of the double-stranded oligonucleotide or the oligonucleotide conjugate. In some embodiments, the pharmaceutically acceptable salt of the double-stranded oligonucleotide or the oligonucleotide conjugate is a mixture of a methylamine salt and an ammonium salt of the double-stranded oligonucleotide or the oligonucleotide conjugate. Pharmaceutical composition In another aspect, the present disclosure also provides a pharmaceutical composition comprising one or more of the single-stranded oligonucleotide, the double-stranded oligonucleotide, the oligonucleotide conjugate, and the pharmaceutically acceptable salt provided by the present disclosure, and a pharmaceutically acceptable excipient. The pharmaceutically acceptable excipient is one or more of various ingredients conventionally employed in the art, such as one or more of a solvent, a protective agent, an osmotic pressure adjusting agent, and other pharmaceutically acceptable carriers. For example, when the pharmaceutical composition is an injection solution, the pharmaceutically acceptable excipient is a solvent, such as one or more of deionized water, water for injection, a pH buffer, physiological saline, ethanol, an aqueous ethanol solution. The pH buffer can be a tris-hydroxymethyl aminomethane hydrochloride buffer having a pH value of 7.5-8.5 and / or a phosphate buffer having a pH value of 5.5-8.5, for example, can be a phosphate buffer having a pH value of 5.5-8.5. The amount of the solvent is adjusted according to the desired concentration of the solution, and the concentration of the oligonucleotide conjugate in the injection solution can be 0.01 mg / mL-20 mg / mL, 0.1 mg / mL-10 mg / mL, or 0.5 mg / mL-5 mg / mL, based on the oligonucleotide group. The protective agent can be at least one of inositol, sorbitol, sucrose, trehalose, mannose, maltose, lactose, and glucose. The protective agent can be contained in an amount of 0.01 to 30% by weight, based on the total weight of the pharmaceutical composition. The osmotic pressure adjusting agent can be sodium chloride and / or potassium chloride. The osmotic pressure adjusting agent can be contained in an amount such that the osmotic pressure of the pharmaceutical composition is 200 to 700 milliosmoles per kilogram (mOsm / kg). The amount of the osmotic pressure adjusting agent can be easily determined by one skilled in the art according to the desired osmotic pressure. In some embodiments, the formulation of the pharmaceutical composition can be adjusted in dosage during administration according to the administration method. In some embodiments, the pharmaceutical composition can be a liquid formulation, such as an injection solution, or a lyophilized powder formulation that is mixed with a liquid excipient to prepare a liquid formulation for administration. The liquid formulation can be, but is not limited to, used for subcutaneous, intramuscular, or intravenous injection, or can be, but is not limited to, delivered to the lung by spraying, or to other organ tissues (e.g., the liver) by spraying through the lung, or by oral administration, etc. In some embodiments, the pharmaceutical composition is administered by subcutaneous injection. The pharmaceutically acceptable additional carrier can be one or more of the carriers conventionally used in the field of double-stranded oligonucleotide administration, such as, but not limited to, magnetic nanoparticles (e.g., nanoparticles based on Fe3O4 or Fe2O3), carbon nanotubes, mesoporous silicon, calcium phosphate nanoparticles, polyethylenimine (PEI), polyamidoamine (PAMAM) dendrimer, poly(L-lysine) (PLL), chitosan, 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), poly(D&L-lactic / glycolic acid) copolymer (PLGA), poly(2-aminoethyl ethylene phosphate) (PPEEA), and poly(2-dimethylaminoethyl methacrylate) (PDMAEMA), and derivatives thereof. In some embodiments, the pharmaceutical composition does not have a specific requirement for the content of the oligonucleotide and the pharmaceutically acceptable carrier, and in some embodiments, the weight ratio of the oligonucleotide or the oligonucleotide conjugate to the pharmaceutically acceptable carrier can be 1 : (1-500), and in some embodiments, the weight ratio is 1 : (1-50). In some embodiments, the pharmaceutical composition can be in the form of a liposome preparation. In some embodiments, the pharmaceutically acceptable carrier used in the liposome preparation comprises an amine-containing transfection compound (hereinafter can also be referred to as an organic amine), a helper lipid, and / or a pegylated lipid. Among them, the organic amine, the helper lipid, and the pegylated lipid can be selected from one or more of the amine-containing transfection compounds or pharmaceutically acceptable salts or derivatives thereof, the helper lipids, and the pegylated lipids described in Chinese Patent Application CN103380113A (which is incorporated herein by reference in its entirety). In some embodiments, the organic amine can be a compound represented by formula (201) or a pharmaceutically acceptable salt thereof described in Chinese Patent Application CN103380113A: wherein: X 101 and X 102 each independently is O, S, N-A, or C-A, wherein A is hydrogen or a C1-C 20 hydrocarbon chain; Y 101 and Z 101 each independently is C=O, C=S, S=O, CH-OH, or SO2; R 101 , R 102 , R 103 , R 104 , R 105 , R 106 and R 107 each independently is hydrogen, a cyclic or acyclic, substituted or unsubstituted, branched or straight chain aliphatic group, a cyclic or acyclic, substituted or unsubstituted, branched or straight chain heteroaliphatic group, a substituted or unsubstituted, branched or straight chain acyl group, a substituted or unsubstituted, branched or straight chain aryl group, a substituted or unsubstituted, branched or straight chain heteroaryl group; x is an integer from 1 to 10; n is an integer from 1 to 3, m is an integer from 0 to 20, and p is 0 or 1; wherein, if m=p=0, R 102 is hydrogen; and, if at least one of n or m is 2, R 103and the nitrogen in formula (201) forms a structure as shown in formula (202) or formula (203): wherein g, e, and f are each independently an integer from 1 to 6, "HCC" represents a hydrocarbon chain, and each *N represents a nitrogen atom in formula (201). In some embodiments, R 103 is a polyamine. In other embodiments, R 103 is a ketal. In some embodiments, R 101 and R 102 each independently is any substituted or unsubstituted, branched or straight chain alkyl or alkenyl group having from 3 to about 20 carbon atoms, such as from 8 to about 18 carbon atoms, and from 0 to 4 double bonds, such as from 0 to 2 double bonds. In some embodiments, if each of n and m independently has a value of 1 or 3, then R 103 may be any one of the following formula (204) - formula (213): wherein in formula (204) - formula (213), g, e, and f are each independently an integer from 1 to 6, each "HCC" represents a hydrocarbon chain, and each * shows a possible point of attachment to the nitrogen atom in formula (201), wherein each H at any * position can be replaced to achieve attachment to the nitrogen atom in formula (201). 103 A person skilled in the art can obtain the compound shown in formula (201) by any reasonable method. In some embodiments, the compound shown in formula (201) can be prepared according to the description in Chinese Patent Application CN103380113A. In some embodiments, the organic amine is an organic amine as shown in formula (214) and / or an organic amine as shown in formula (215): the helper lipid is cholesterol, an analog of cholesterol, and / or a derivative of cholesterol; the pegylated lipid is 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethylene glycol)]-2000. In some embodiments, the molar ratio among the organic amine, the helper lipid, and the pegylated lipid in the pharmaceutical composition is (19.7-80):(19.7-80):(0.3-50), for example, can be (50-70):(20-40):(3-20). ​In some embodiments, the pharmaceutical composition particles formed from the oligonucleotide or oligonucleotide conjugate of the present disclosure and the above-mentioned amine-containing transfection reagent have an average diameter of about 30 nm to about 200 nm, typically about 40 nm to about 135 nm, more typically, the average diameter of the liposome particles is about 50 nm to about 120 nm, about 50 nm to about 100 nm, about 60 nm to about 90 nm, or about 70 nm to about 90 nm, for example, the average diameter of the liposome particles is about 30, 40, 50, 60, 70, 75, 80, 85, 90, 100, 110, 120, 130, 140, 150, or 160 nm. In some embodiments, in the pharmaceutical composition formed from the oligonucleotide or oligonucleotide conjugate of the present disclosure and the above-mentioned amine-containing transfection reagent, the weight ratio (weight / weight ratio) of the oligonucleotide or oligonucleotide conjugate to the total lipids (e.g., organic amine, helper lipid, and / or PEGylated lipid) is in the range of from about 1:1 to about 1:50, from about 1:1 to about 1:30, from about 1:3 to about 1:20, from about 1:4 to about 1:18, from about 1:5 to about 1:17, from about 1:5 to about 1:15, from about 1:5 to about 1:12, from about 1:6 to about 1:12, or from about 1:6 to about 1:10, for example, the weight ratio of the oligonucleotide or oligonucleotide conjugate of the present disclosure to the total lipids is about 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, or 1:18. In some embodiments, the components of the pharmaceutical composition can exist independently at the time of sale and in the form of a liquid preparation at the time of use. In some embodiments, the pharmaceutical composition formed from the oligonucleotide or oligonucleotide conjugate of the present disclosure and the above-mentioned pharmaceutically acceptable carrier can be prepared according to various known methods, except that the existing siRNA is replaced with the oligonucleotide or oligonucleotide conjugate of the present disclosure; in some embodiments, it can be prepared according to the following method: The organic amine, helper lipid, and PEGylated lipid are suspended in alcohol in the above-mentioned molar ratio and mixed to obtain a lipid solution; the amount of alcohol is such that the total mass concentration of the obtained lipid solution is 2-25 mg / mL, for example, it can be 8-18 mg / mL. The alcohol is selected from pharmaceutically acceptable alcohols, such as alcohols that are liquid near room temperature, for example, one or more of ethanol, propylene glycol, benzyl alcohol, glycerol, polyethylene glycol 200, polyethylene glycol 300, polyethylene glycol 400, for example, it can be ethanol. The oligonucleotide or oligonucleotide conjugate provided by the present disclosure is dissolved in a buffer salt solution to obtain an aqueous solution of the oligonucleotide or oligonucleotide conjugate. The concentration of the buffer salt solution is 0.05-0.5M, for example, it can be 0.1-0.2M, the pH of the buffer salt solution is adjusted to 4.0-5.5, for example, it can be 5.0-5.2, and the amount of the buffer salt solution is such that the concentration of the oligonucleotide in the oligonucleotide or oligonucleotide conjugate is not more than 0.6mg / mL, for example, it can be 0.2-0.4mg / mL. The buffer salt is selected from one or more of soluble acetate, soluble citrate, for example, it can be sodium acetate and / or potassium acetate. The lipid solution and the aqueous solution of the oligonucleotide or oligonucleotide conjugate are mixed, and the product obtained after mixing is incubated at 40-60℃ for at least 2 minutes, for example, it can be 5-30 minutes, to obtain the liposome preparation after incubation. The volume ratio of the lipid solution to the aqueous solution of the oligonucleotide or oligonucleotide conjugate is 1:(2-5). The liposome preparation after incubation is concentrated or diluted, impurities are removed, and sterilization is performed to obtain the pharmaceutical composition provided by the present disclosure, which has the following physicochemical parameters: pH value of 6.5-8, encapsulation efficiency of not less than 80%, particle size of 40-200nm, polydispersity index of not more than 0.30, and osmotic pressure of 250-400mOsm / kg; for example, the physicochemical parameters can be: pH value of 7.2-7.6, encapsulation efficiency of not less than 90%, particle size of 60-100nm, polydispersity index of not more than 0.20, and osmotic pressure of 300-400mOsm / kg. The concentration or dilution can be performed before, after or simultaneously with the removal of impurities. The method for removing impurities can use various existing methods, for example, a tangential flow system or a hollow fiber column can be used, and ultrafiltration is performed under the condition of 100K Da, and the ultrafiltration exchange solution is a phosphate buffer solution (PBS) with pH 7.4. The method for sterilization can use various existing methods, for example, sterilization can be performed by filtering through a 0.22μm filter. Applications of the single-stranded oligonucleotide, double-stranded oligonucleotide, oligonucleotide conjugate, pharmaceutically acceptable salt and pharmaceutical composition of the present disclosure The present disclosure also provides the use of one or more of the single-stranded oligonucleotide of the present disclosure, the double-stranded oligonucleotide of the present disclosure, the oligonucleotide conjugate of the present disclosure, the pharmaceutically acceptable salt of the present disclosure and the pharmaceutical composition of the present disclosure in a medicament for treating and / or preventing a disease or symptom related to the level of CFB mRNA. In some embodiments, the disease or condition associated with CFB mRNA levels is selected from one or more of primary membranous nephropathy, hemolytic uremic syndrome, C3 glomerulopathy, IgA nephropathy, diabetic nephropathy, polycystic kidney disease, membranous nephropathy, paroxysmal nocturnal hemoglobinuria (PNH), myasthenia gravis (MG), age-related macular degeneration, an ophthalmic disease, and rheumatoid arthritis. In some embodiments, the disease or condition associated with CFB mRNA levels is selected from one or more of C3 glomerulopathy, myasthenia gravis (MG), IgA nephropathy, diabetic nephropathy, and polycystic kidney disease. The present disclosure also provides a method of treating and / or preventing a disease or condition associated with CFB mRNA levels, the method comprising administering to a subject in need thereof an effective amount of a double-stranded oligonucleotide and / or oligonucleotide conjugate of the present disclosure and / or a pharmaceutical composition of the present disclosure. Further, the present disclosure also provides a method of modulating the level of CFB mRNA expression in a cell, the method comprising contacting an effective amount of a double-stranded oligonucleotide and / or oligonucleotide conjugate and / or pharmaceutically acceptable salt and / or pharmaceutical composition of the present disclosure with the cell. The term "administering / administration" as used herein refers to the placement of one or more of a single-stranded oligonucleotide, a double-stranded oligonucleotide, an oligonucleotide conjugate, a pharmaceutically acceptable salt, and a pharmaceutical composition of the present disclosure into the body of a subject by a method or route that results in at least partial localization of the one or more of the single-stranded oligonucleotide, the double-stranded oligonucleotide, the oligonucleotide conjugate, the pharmaceutically acceptable salt, and the pharmaceutical composition to the desired site to produce the desired effect. Routes of administration suitable for the methods of the present disclosure include local administration and systemic administration. In general, local administration results in delivery of more of the one or more of the single-stranded oligonucleotide, the double-stranded oligonucleotide, the oligonucleotide conjugate, the pharmaceutically acceptable salt, and the pharmaceutical composition to a particular site as compared to the entire body of the subject; whereas systemic administration results in delivery of the one or more of the single-stranded oligonucleotide, the double-stranded oligonucleotide, the oligonucleotide conjugate, the pharmaceutically acceptable salt, and the pharmaceutical composition to substantially the entire body of the subject. Administration to a subject can be by any suitable route known in the art, including but not limited to oral or parenteral routes, such as intravenous administration, intramuscular administration, subcutaneous administration, transdermal administration, airway administration (aerosol), pulmonary administration, nasal administration, rectal administration, and topical administration (including buccal administration and sublingual administration). The frequency of administration can be one or more times per day, per week, per two weeks, per three weeks, per month, or per year. The dosage of one or more of the single stranded oligonucleotides, double stranded oligonucleotides, oligonucleotide conjugates, pharmaceutically acceptable salts, and pharmaceutical compositions described herein can be a conventional dosage in the art, which can be determined based on various parameters, particularly the age, body weight, and gender of the subject. Toxicity and therapeutic efficacy of such compounds can be determined by standard pharmaceutical procedures in cell cultures or experimental animals, e.g., by determining the LD50 (the dose lethal to 50% of the population) and the ED50 (the dose therapeutically effective in 50% of the population). The dosage regimen can be planned based on the data obtained from these Upon administration of the single stranded oligonucleotides, double stranded oligonucleotides, oligonucleotide conjugates, pharmaceutically acceptable salts, and / or pharmaceutical compositions described herein, for example, to a male or female, 6-12 week old, 18-25 g body weight C57BL / 6J or C3H / HeNCrlVr mouse, the amount of siRNA in the siRNA, pharmaceutical composition, and / or siRNA conjugate can be 0.001-100 mg / kg body weight, in some embodiments 0.01-50 mg / kg body weight, in further embodiments 0.05-20 mg / kg body weight, in still further embodiments 0.1-15 mg / kg body weight, and in yet further embodiments 0.1-10 mg / kg body weight, of siRNA in the siRNA conjugate formed by the siRNA and the pharmaceutically acceptable conjugate molecule. The above amounts can be preferred upon administration of the siRNA, pharmaceutical composition, and / or siRNA conjugate described herein. The amount of double stranded oligonucleotide in one or more of the oligonucleotides, oligonucleotide conjugates, pharmaceutically acceptable salts, and pharmaceutical compositions provided herein to inhibit expression of CFB mRNA in a cell using the methods provided herein is readily determined by one of skill in the art based on the desired effect. For example, in some embodiments, the oligonucleotide is an siRNA, the oligonucleotide conjugate is an siRNA conjugate, and the amount of siRNA in the siRNA conjugate provided is an amount sufficient to reduce CFB mRNA levels and result in an extracellular concentration of 1 pM to 1 mM, or 0.01 nM to 100 nM, or 0.05 nM to 50 nM, or to about 5 nM at the surface of the target cell. The amount required to achieve this local concentration will vary depending on various factors, including the method of delivery, the site of delivery, the number of cell layers between the site of delivery and the target cell or tissue, whether the delivery is local or systemic, etc. The concentration at the site of delivery can be significantly higher than the concentration at the surface of the target cell or tissue. Kits The present disclosure provides a kit comprising the single-stranded oligonucleotide, double-stranded oligonucleotide, oligonucleotide conjugate, pharmaceutically acceptable salt, and / or oligonucleotide conjugate provided herein. In some embodiments, the kits described herein can provide the single-stranded oligonucleotide, double-stranded oligonucleotide, oligonucleotide conjugate, pharmaceutical composition, pharmaceutically acceptable salt, and / or oligonucleotide conjugate in one container. In some embodiments, the kits described herein can comprise one container providing a pharmaceutically acceptable excipient. In some embodiments, the kits can further comprise other ingredients such as stabilizers or preservatives, etc. In some embodiments, the kits described herein can comprise at least one other therapeutic agent in a container different from the container providing one or more of the single-stranded oligonucleotide, double-stranded oligonucleotide, oligonucleotide conjugate, pharmaceutically acceptable salt, and pharmaceutical composition described herein. In some embodiments, the kits can comprise instructions for admixing the single-stranded oligonucleotide, double-stranded oligonucleotide, oligonucleotide conjugate, pharmaceutically acceptable carrier, and / or excipient or other ingredients, if any. In the kits of the present disclosure, one or more of the single-stranded oligonucleotide, double-stranded oligonucleotide, oligonucleotide conjugate, pharmaceutically acceptable salt, and pharmaceutical composition, and / or pharmaceutically acceptable excipient can be provided in any form, such as liquid form, dry form, or lyophilized form. In some embodiments, one or more of the single-stranded oligonucleotide, double-stranded oligonucleotide, oligonucleotide conjugate, pharmaceutically acceptable salt, and pharmaceutical composition, and optional pharmaceutically acceptable excipient are substantially pure and / or sterile. In some embodiments, sterile water can be provided in the kits of the present disclosure. The present disclosure will be further described by way of Examples below, but the present disclosure is not in any way limited thereto. Without wishing to be limited, the present application is further described in detail in the following embodiments and examples of exemplary embodiments of double-stranded oligonucleotides in the pharmaceutical compositions, oligonucleotides and / or oligonucleotide conjugates of the present disclosure, which are exemplary embodiments of small interfering RNA (siRNA). In this case, the double-stranded oligonucleotides, the pharmaceutical compositions and the oligonucleotide conjugates of the present disclosure are siRNA, the pharmaceutical compositions comprising siRNA and the siRNA conjugates, respectively. In the context of the present disclosure, for ease of description, the siRNA, the pharmaceutical compositions comprising siRNA and the siRNA conjugates in these embodiments are also referred to as siRNA of the present disclosure, the pharmaceutical compositions of the present disclosure and the siRNA conjugates of the present disclosure. This does not mean that the double-stranded oligonucleotides of the present disclosure can only be siRNA, on the contrary, the double-stranded oligonucleotides can be other variants disclosed herein or known to those skilled in the art, such as small activating RNA (saRNA) and the like. It is envisaged that based on the detailed description of siRNA, the pharmaceutical compositions comprising siRNA and the siRNA conjugates, other double-stranded oligonucleotides will similarly function when used alone, or form the pharmaceutical compositions and / or oligonucleotide conjugates described in the present disclosure. Examples Unless otherwise specified, the reagents, media used in the following examples are commercially available, and the nucleic acid electrophoresis, real-time PCR and other operations are carried out according to the methods described in Molecular Cloning (Cold Spring Harbor Laboratory Press (1989)). Preparation Example 1 Synthesis of siRNA conjugates 1-44 provided by the present disclosure According to the preparation method described in CN110959011A Preparation Example 13, the following conjugates 1-44 in Table 2A were prepared, the only difference being that the sense strand and the antisense strand of the siRNA contained in each siRNA conjugate are as shown in Table 2A; for the nucleic acid sequences with the sense strand and the antisense strand of the siRNA numbered as conjugates 1-44 in Table 2A below, the nucleoside phosphoramidite monomers were connected one by one to synthesize the sense strand and the antisense strand of the siRNA conjugate. After the synthesis was completed, 3K (MWCO) ultrafiltration tube was used for centrifugal ultrafiltration desalination purification. Conjugate 1-44 is a mixture of methylamine salt and ammonium salt of a compound having a structure shown in formula (403), wherein the P atom shown in formula (403) is covalently linked to the oxygen atom of the inverted deoxy abasic nucleotide (ia) shown in formula (35) connected to the ribose ring by a methylene group at the 3' end of the sense strand of the siRNA represented by Nu, thereby covalently linked to the sense strand of the siRNA. And the siRNA contained in the siRNA conjugate has the siRNA sequence corresponding to Conjugate 1-44 in Table 2A. Table 2A siRNA sequence in siRNA conjugate wherein, capital letters C, G, U, A and T represent the base composition of the nucleotide; the lower case letter m represents that the nucleotide represented by the capital letter adjacent to the left of the letter m is a 2'-methoxy modified nucleotide; the lower case letter f represents that the nucleotide represented by the capital letter adjacent to the left of the letter f is a 2'-fluoro modified nucleotide; the lower case letter s represents that the nucleotides represented by the two capital letters adjacent to the left and right of the letter s are connected by a phosphorothioate group; the lower case letter d represents that the nucleotide represented by the capital letter adjacent to the right of the letter d is a deoxyribonucleotide; ia represents an inverted abasic deoxyribonucleotide; and the letter combination VP represents that the nucleotide represented by the capital letter adjacent to the right of the letter combination is a 5'-VP modified nucleotide. After each siRNA conjugate was diluted to a concentration of 0.2 mg / mL (calculated as siRNA) using ultrapure water (Milli-Q ultrapure water instrument, resistivity 18.2 MΩ*cm (25℃)), the molecular weight was detected by liquid chromatography-mass spectrometry (LC-MS, Liquid Chromatography-Mass Spectrometry, purchased from Waters Company, model: LCT Premier). The specific molecular weight detection results are shown in Table 2B below. Table 2B siRNA conjugate molecular weight detection results The measured value is consistent with the theoretical value, indicating that the synthesized conjugate 1-44 contains the target designed double-stranded nucleic acid sequence. Preparation of Comparative Conjugate 1 of Comparative Preparation Example 1 The phosphoramidite intermediate shown in formula (1008b) was prepared according to the method of Example 2 of CN109462981A1. Reference Conjugate 1 was prepared by solid phase synthesis method using the phosphoramidite intermediate as shown in formula (1008b) as starting material. After the synthesis was completed, the product was purified by centrifugal ultrafiltration desalination using 3K (MWCO) ultrafiltration tube. Reference Conjugate 1 is a mixture of methylamine salt and ammonium salt of a compound having the structure shown in formula (1008a), wherein the conjugate group is attached to the ribose 5' position of the 5' terminal nucleotide of the antisense strand of siRNA represented by Nu. The sense and antisense strands of the siRNA contained in Reference Conjugate 1 have the sequences shown in SEQ ID NO: 106 and SEQ ID NO: 105, respectively. UmsAfsAmGmUmAmCfUmCmAmGmAfCmAfCmUfAmCmAmGmsCm (SEQ ID NO: 105); (ia) sGmCmUmGmUmGmGmUmGfUfCfUmGmAmGmUmAmCmUmUmAms (ia) (SEQ ID NO: 106). After each siRNA conjugate was diluted to a concentration of 0.2 mg / mL (calculated as siRNA) using ultrapure water (Milli-Q ultrapure water instrument, resistivity 18.2 MΩ*cm (25℃)), the molecular weight was detected using a liquid chromatograph-mass spectrometer (LC-MS, Liquid Chromatography-Mass Spectrometry, purchased from Waters Company, model: LCT Premier). The results were as follows: the theoretical value of the sense strand: 6945.7, the measured value of the sense strand: 6944.9; the theoretical value of the antisense strand: 8709.1, the measured value of the antisense strand: 8708.0. The measured value was consistent with the theoretical value, indicating that the synthesized reference conjugate 1 contained the double-stranded nucleic acid sequence and conjugate structure designed as the target. Reference Conjugate 1 is the preferred siRNA conjugate targeting CFB disclosed in the prior art. Synthesis of Reference Conjugate 2 of Comparative Preparation Example 2 Reference the preparation method of WO2022076922A1 Example 9, the phosphoramidite intermediate as shown in formula (500) was prepared by the following synthetic route. The difference is that step E-5 uses 2-bromo-N-2-propyn-1-ylacetamide (CAS: 173208-24-7, as shown in formula (500-8)) instead of 3-bromopropynyl (as shown in formula (500-9)) used in WO2022076922A1 Example 9; referring to the preparation method of compound 9 in WO2022076922A1 Example 9, the difference is that the phosphoramidite intermediate with the structure shown in formula (500) is formed by connecting formula (500-7) with N,N-diisopropyl chlorophosphoramidite (2-cyanoethyl) ester (CAS: 89992-70-1, as shown in formula (500-10)). The intermediate shown in formula (501) is prepared by solid-phase synthesis method using the phosphoramidite intermediate shown in formula (500) as raw material, and the nucleoside monomers are connected one by one according to the sequence of the antisense strand of the siRNA described in the present disclosure. Further, referring to the preparation method of Example 9 of WO2022076922A1, the specific synthesis route of reference conjugate 2 is as follows: After the synthesis is completed, 3K (MWCO) ultrafiltration tube is used for centrifugal ultrafiltration desalination purification. The reference conjugate 2 is a mixture of methylamine salt and ammonium salt of the compound with the structure shown in formula (503), wherein the P atom shown in formula (503) is connected to the ribose 5' position of the 5' terminal nucleotide of the antisense strand of the siRNA represented by Nu through a covalent bond. And the sense strand and the antisense strand of the siRNA contained in the reference conjugate 2 are respectively the sequences shown in SEQ ID NO: 108 and SEQ ID NO: 107. 5'-GmGmAmAmGmGmAmUfUmAfUfCfUfGmGmAmUmGmUmCmUmsAmsia-3' (SEQ ID NO: 108); 5'-UmsAfsGmAfCmAfUmCfCmAfGmAfUmAfAmUfCmCfUmUfsCmsCm-3' (SEQ ID NO: 107) The reference conjugate 2 is an siRNA conjugate with very similar siRNA sequence (the antisense strand sequence is the same, and the sense strand sequence is slightly different) to the conjugate 33, but with different modification methods. After each siRNA conjugate was diluted to a concentration of 0.2 mg / mL (calculated as siRNA) using ultrapure water (Milli-Q ultrapure water instrument, resistivity 18.2 MΩ*cm (25 °C)), the molecular weight was detected using a liquid chromatograph-mass spectrometer (LC-MS, purchased from Waters Company, model: LCT Premier). The results were as follows: the theoretical value of the sense strand: 7158.6, the measured value of the sense strand: 7157.8; the theoretical value of the antisense strand: 9626.0, the measured value of the antisense strand: 9624.3. The measured value was consistent with the theoretical value, indicating that the synthesized reference conjugate 2 contained the double-stranded nucleic acid sequence and the conjugate structure designed. Inhibitory activity of the conjugate of the present disclosure in vitro This experimental example investigated the inhibitory activity of conjugate 1-25 on CFB mRNA in the liver primary cells of hCFB transgenic mice in vitro. The specific steps were as follows: [1] Cell culture Mouse liver primary cells were obtained by extracting fresh liver tissue from human CFB transgenic mice (6 weeks old, purchased from Shanghai Southern Model Organism Technology Co., Ltd.) and adjusting the density of the mouse liver primary cells to 1.0 x 10 5 cells / mL in Opti-MEM (1X) medium (GIBCO Company, item number 31985-70) to obtain a mouse liver primary cell suspension. The mouse liver primary cell suspension was inoculated into a 12-well plate at a density of 1.0 x 10 5 cells / well, 1 mL of cell solution per well, and continued to be cultured for 1.5 h. [2] Transfection For each siRNA conjugate to be tested, an siRNA conjugate working solution was prepared using PBS at a concentration of 20 μM (calculated as the amount of siRNA in the conjugate). The siRNA conjugates to be tested used were conjugates 1-25. For each siRNA conjugate to be tested, a 1A solution was prepared, and each 1A solution contained 3 μL of the siRNA conjugate working solution and 97 μL of the cell maintenance medium. For each siRNA conjugate to be tested, a 1B solution was prepared, and each 1B solution contained 2 μL of Lipofectamine TM RNAiMAX (Invitrogen Company) and 98 μL of Opti-MEM medium. For each siRNA conjugate to be tested, one portion of solution 1A and one portion of solution 1B were mixed, and the transfection complex X1 was obtained by incubation at room temperature for 20 min. In each culture well (all of which contained the hCFB transgenic mouse liver primary cells and 1 mL of Opti-MEM medium, as described above), the transfection complex X1 of each siRNA conjugate was added, and the mixture was mixed evenly, with an amount of 200 μL / well, to obtain a transfection mixture with a concentration of 50 nM (calculated based on the amount of siRNA, as described below) of each siRNA conjugate. The transfection complex X1 of each siRNA conjugate was used to transfect two culture wells, respectively, to obtain the transfection mixture containing the siRNA conjugate, which was denoted as test group X1-X25. One portion of solution 1B was mixed with 100 μL of cell maintenance medium to obtain a blank transfection mixture B. In another two culture wells, the blank transfection mixture B was added, with an amount of 200 μL / well, to obtain the transfection mixture without the siRNA conjugate, which was denoted as the blank control group. After 4 h, 1 mL of DMEM medium containing 10% fetal bovine serum was added to each well. The above test groups X1-X25 and the blank control group were placed in an incubator under an atmosphere of air containing 5% CO2, and incubation was continued at 37°C for 24 h. [3] Detection Total RNA in the cells was extracted using Trizol (Sigma) according to the standard operation procedure for total RNA extraction. For each well of cells, 1 μg of total RNA was taken, and reverse transcription was performed on the total RNA of each well of cells using a reverse transcription kit (Reverse Transcription System, purchased from Promega, item number A3500) according to the reagent provided in the kit, in which Oligo(dT) was selected as the primer, and a reverse transcription reaction system 20 μL was configured according to the reverse transcription operation procedure in the kit instructions. The reverse transcription conditions were as follows: for each reverse transcription reaction system, the reverse transcription reaction system was incubated at 70°C for 10 min, then at 42°C for 30 min, and finally at 95°C for 5 min. After the reaction was completed, 80 μL of DEPC water was added to the reverse transcription reaction system to obtain a solution containing cDNA. For each reverse transcription reaction system, 5 μL of the above solution containing cDNA was taken as a template, and SYBR TMGreen Universal Premix Kit (purchased from Applied Biosystems, item number 4309155) provides reagents for configuring a qPCR reaction system of 20 μL, wherein the PCR primer sequences for amplifying the target gene CFB and the internal reference gene GAPDH are shown in Table 3, and the final concentration of each primer is 10 μM. Each qPCR reaction system is placed on an ABI StepOnePlus Real-Time PCR instrument, and a three-step method is used for amplification, with the amplification procedure being 95 °C pre-denaturation for 10 min, followed by 95 °C denaturation for 30 s, 60 °C annealing for 30 s, 72 °C extension for 30 s, and repeating the above denaturation, annealing, and extension processes for 40 times, to obtain product W1 containing the products of the amplified target gene CFB and the internal reference gene GAPDH. Product W1 is then subjected to 95 °C for 15 s, 60 °C for 1 min, gradient heating to 95 °C with the fluorescence signal being collected every 0.3 °C, 95 °C for 15 s, and real-time fluorescence quantitative PCR instrument to collect the melting curves of the target gene and the internal reference gene GAPDH in product W1, to obtain the Ct values of the target gene CFB and the internal reference gene GAPDH. Table 3 Primer information The comparative Ct (ΔΔCt) method is used to perform relative quantitative calculation on the expression level of the target gene CFB mRNA in each test group, and the calculation method is as follows: ΔCt (test group) = Ct (test group target gene) - Ct (test group internal reference gene) ΔCt (control group) = Ct (control group target gene) - Ct (control group internal reference gene) ΔΔCt (test group) = ΔCt (test group) - ΔCt (control group average) ΔΔCt (control group) = ΔCt (control group) - ΔCt (control group average) Wherein, ΔCt (control group average) is the arithmetic mean of ΔCt (control group) of each culture well of the control group. Thus, each culture well of the test group and the control group corresponds to a ΔΔCt value. The expression level of CFB mRNA in the test group is normalized based on the average value of the control group, and the average value of the expression level of CFB mRNA in the control group is defined as 100%, Relative expression level of CFB mRNA in the test group = 2-ΔΔCt (test group) x 100% Inhibition rate of CFB mRNA in the test group = (1-relative expression level of CFB mRNA in the test group) x 100% The experimental results are shown in Table 4 below. Table 4 Inhibition activity of siRNA conjugates in hCFB transgenic mouse liver primary cells Table 4 shows the relative inhibition rate of CFB mRNA in hCFB transgenic mouse liver primary cells in vitro after transfection of 50 nM of siRNA conjugates of the present disclosure. The results show that all the siRNA conjugates tested exhibit excellent inhibitory effect at a concentration of 50 nM in hCFB transgenic mouse liver primary cells in vitro, with CFB mRNA inhibition rate of more than 87%; further, among the 25 different conjugates, as high as 14 achieve CFB mRNA inhibition rate of more than 95% at the same concentration; this result embodies the high-efficiency inhibitory effect of siRNA conjugates of the present disclosure on CFB gene expression. Experimental Example 2 CFB mRNA inhibitory activity of siRNA conjugates of the present disclosure in vitro This experimental example investigates the CFB mRNA inhibitory activity of siRNA conjugates of the present disclosure in hCFB transgenic mouse liver primary cells in vitro at concentrations of 5 nM and 0.5 nM. [1] Cell culture The mouse liver primary cell suspension was obtained using the same method as in Experimental Example 1. Then the obtained mouse liver primary cell suspension was inoculated into 12-well plates at 1.0 x 10 5 The cells were inoculated into 12-well plates at 1.0 x 10 [2] Transfection For each siRNA conjugate, 2 μM and 0.2 μM siRNA conjugate working solutions were prepared with PBS, respectively. The conjugates used were conjugates 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 18, 21, 22, 23, 24 and 25, respectively. For each siRNA conjugate, 2A1 solution was prepared, with each 2A1 solution containing 3 μL of siRNA conjugate working solution at a concentration of 2 μM and 97 μL of cell maintenance medium. For each siRNA conjugate, 2A2 solution was prepared, with each 2A2 solution containing 3 μL of siRNA conjugate working solution at a concentration of 0.2 μM and 97 μL of cell maintenance medium. For each siRNA conjugate, 2B solution was prepared, with each 2B solution containing 2 μL of Lipofectamine TM RNAiMAX (Invitrogen Corporation) and 98 μL of Opti-MEM medium. For each siRNA conjugate, one portion of 2A1 solution and one portion of 2B solution were mixed, respectively, to obtain transfection complex 2X aIn the culture wells (all of which are the above-described culture wells containing the hCFB transgenic mouse liver primary cells and 1 mL of Opti-MEM medium, the same below); 2X a , mixed evenly, and added in an amount of 200 μL / well to obtain a transfection mixture with a concentration of 5 nM (calculated based on the amount of siRNA, the same below). Two culture wells were respectively transfected with the transfection mixture containing the siRNA conjugate, and recorded as Test Group 2X a -2X a1 -2X a16 . For each siRNA conjugate, one portion of the 2A2 solution and one portion of the 2B solution were mixed, and incubated at room temperature for 20 min to obtain a transfection complex 2X b In the culture wells (all of which are the above-described culture wells containing the hCFB transgenic mouse liver primary cells and 1 mL of Opti-MEM medium, the same below), the transfection complex of each siRNA conjugate was added respectively 2X b , mixed evenly, and added in an amount of 200 μL / well to obtain a transfection mixture with a concentration of 0.5 nM (calculated based on the amount of siRNA, the same below). Two culture wells were respectively transfected with the transfection mixture containing the siRNA conjugate, and recorded as Test Group 2X b -2X b1 -2X b16 . The 2X0 solution was prepared by mixing one portion of the 2B solution with 100 μL of cell maintenance medium, and incubating at room temperature for 20 min to obtain a blank transfection complex 2X0. In another two culture wells, the blank transfection mixture 2B was added respectively in an amount of 200 μL / well to obtain a transfection mixture without the siRNA conjugate, and recorded as the blank control group. The above Test Group Test Group 2X a1 -2X a16 , 2X b1 -2X b16 and the blank control group were placed in an incubator with an atmosphere of 5% CO2at 37°C for further culture for 24 h. The total RNA in each well was extracted and reverse transcribed by using the same method as in Experimental Example 1, and the relative quantification of the target gene CFB mRNA in each test group was calculated. The results are shown in Table 5 below. Table 5 Inhibitory activity of conjugates at different concentrations in hCFB transgenic mouse liver cells Table 5 shows the relative inhibition rate of CFB mRNA in hCFB transgenic mouse liver primary cells in vitro after transfection of 5 nM and 0.5 nM siRNA conjugates of the present disclosure. The results show that all the siRNA conjugates tested exhibit excellent inhibition effect at a concentration of 5 nM in hCFB transgenic mouse liver primary cells in vitro, with CFB mRNA inhibition rate of more than 86%; and most of the conjugates have more than 90% CFB mRNA inhibition rate. At the same time, the conjugates of the present disclosure also show good effect of inhibiting CFB mRNA expression at a low concentration of 0.5 nM, with the lowest inhibition rate of 66.0%, and even up to 86.5%. Experimental Example 3 siRNA conjugate in vivo activity test This experimental example investigates the inhibition effect of the conjugates of the present disclosure in mice in vivo. The conjugates 1, 3, 4, 8, 9, 11, 23, 25 and 26 were dissolved in PBS to a concentration of 0.6 mg / mL (calculated by the amount of siRNA) respectively. Fifty mice (human CFB transgenic mice, grade: SPF, week age: 6-8 weeks, purchased from Shanghai South Model Organisms Technology Co., Ltd.) were randomly divided into 10 groups according to 5 mice / group, and each group was randomly divided according to body weight, and were recorded as test groups 1-9 and a blank control group. The mice in test groups 1-9 were given 0.6 mg / mL of the above conjugate solution by subcutaneous injection in the abdomen; the mice in the blank group were given PBS solution. The mice in each group were weighed and recorded before administration, and the administration was given according to the body weight, and the single administration amount was 5 mL / Kg of mouse body weight. The corresponding conjugate numbers of each test group and control group are shown in Table 6. The blood of mice in vivo was collected at the 8th day, 15th day, 22nd day and 29th day after administration of conjugate 1, conjugate 3, conjugate 4, conjugate 9 and conjugate 25; at the 8th day, 15th day, 22nd day, 29th day, 36th day, 43rd day, 50th day and 57th day after administration of conjugate 8, conjugate 11, conjugate 23 and conjugate 26, taking the administration time point as the 1st day, and the expression amount of hCFB protein in the serum of mice in the test group and control group was detected by using a kit (purchased from Abeam Company) according to the operation instruction, and the expression amount of hCFB protein in the serum of mice was normalized to 100% of the expression amount of hCFB protein in the serum of mice before administration of the blank group to obtain the inhibition rate of the expression amount of hCFB protein in the serum of mice. The relative level of serum hCFB protein was calculated according to the following equation: The relative level of serum hCFB protein = (the serum hCFB protein level of the test group / the average value of the serum hCFB protein level of the control group) x 100%. Serum hCFB protein inhibition rate = 100% - serum hCFB protein relative level. After D29 detection, the groups of conjugate 1, conjugate 2, conjugate 3, and conjugate 8, which had an inhibition rate less than 70%, were no longer subjected to subsequent serum protein level detection; after D36 detection, the group of conjugate 5 was no longer subjected to subsequent serum protein level detection. The results are shown in Table 6. Table 6: hCFB protein inhibition rate in mice From the results in Table 6, it can be observed that in the hCFB transgenic mouse experiment, all the conjugates in the test groups can continuously inhibit the expression of hCFB protein for a long time at a dose of 3 mg / kg of body weight. On day 8, the inhibition rate of the conjugates on hCFB protein in the hCFB transgenic mice was more than 68%, and even reached 88.8%; on day 22, the inhibition rate of conjugate 23 on hCFB protein in the hCFB transgenic mice was still 85.7%; on day 50, the inhibition rate of conjugate 23 on hCFB protein in the hCFB transgenic mice was still as high as 54.9%. Experimental Example 4: siRNA conjugate in vivo activity test in mice This experimental example investigates the inhibitory effect of the conjugates of the present disclosure in mice. The same mice and experimental conditions as in Experimental Example 3 were used, with 4 mice in each group, except that the test conjugates were replaced by conjugate 40, conjugate 41, conjugate 42, conjugate 43, and conjugate 44. Taking the administration time point as day 1, blood was collected from the mice on day 8, day 15, day 29, day 43, and day 57 after administration, and the inhibition rate of hCFB protein expression in the serum of the mice was detected using the same detection method as in Experimental Example 3. The conjugate numbers corresponding to each test group and the control group are shown in Table 7. Table 7: hCFB protein inhibition rate in mice Table 7 shows the inhibition rate of CFB protein in hCFB transgenic mice after administration of siRNA conjugates of the present disclosure at a dose of 3 mg / kg (based on siRNA). The results show that the inhibition rate of hCFB protein of all test conjugates on day 8 and day 15 after administration is more than 80%, and the inhibitory effect lasts until the end of the experiment (D57). Among them, conjugates 42-44 maintain an inhibition rate of at least 54% on day 57. In particular, conjugate 44 maintains an inhibition rate of hCFB protein in hCFB transgenic mice of more than 75% throughout the 57-day test period, with a maximum of 91%. This indicates that the conjugates provided by the present disclosure have long-term inhibition of hCFB protein. Experimental Example 5 siRNA conjugate in vivo activity test in mice This experimental example investigates the inhibitory effect of the conjugates of the present disclosure and the reference conjugates in mice in vivo. The same mice and experimental conditions as in Experimental Example 3 were used, with 4 mice in each group, except that the test conjugate was replaced by conjugate 33, conjugate 44, reference conjugate 1 and reference conjugate 2. The time point of administration was taken as day 1, and blood was collected from the mice on day 15, day 29 and day 43 after administration. The inhibitory rate of hCFB protein expression in the serum of the mice was detected by the same detection method as in Experimental Example 3. The conjugate numbers corresponding to each test group and control group are shown in Table 8. Table 8 Inhibition rate of hCFB protein in mice Table 8 shows the inhibition rate of CFB protein in hCFB transgenic mice after administration of siRNA conjugates of the present disclosure at a dose of 3 mg / kg (calculated as siRNA). As previously described, reference conjugate 1 is an siRNA conjugate with a sequence highly similar to conjugate 33 but different modifications, and reference conjugate 2 is a preferred conjugate disclosed in the prior art. However, the results show that, compared with reference conjugate 1 and reference conjugate 2, conjugate 33 and conjugate 44 provided by the present disclosure have significantly higher inhibition rates of CFB protein in hCFB transgenic mice on day 43, specifically, the inhibition rates of CFB protein in hCFB transgenic mice of reference conjugate 1 and reference conjugate 2 on day 43 are 1.6% and 28.7%, respectively, while conjugate 33 and conjugate 44 still maintain excellent inhibition effect on CFB protein in hCFB transgenic mice on day 43, with inhibition rates of 40.2% and 61.1%, respectively. The above results show that the conjugates provided by the present disclosure can efficiently inhibit CFB protein in hCFB transgenic mice, and are significantly superior to the reference conjugates in terms of long-term inhibition. Experimental Example 6 siRNA conjugate in vivo activity test in mice This experimental example investigates the inhibitory effect of the conjugates of the present disclosure and the reference conjugates in mice in vivo. The same mice and experimental conditions as in Experimental Example 3 were used, with 4 mice in each group, except that the test conjugate was replaced by conjugate 33, conjugate 44, reference conjugate 1 and reference conjugate 2. The time point of administration was taken as day 1, and blood was collected from the mice on day 15, day 29 and day 43 after administration. The inhibitory rate of hCFB protein expression in the serum of the mice was detected by the same detection method as in Experimental Example 3. The blood of the mice was collected at 15 days, 29 days and 43 days after administration, with the administration time point being taken as day 1, and the decrease rate of the expression amount of hCFB protein in the serum of the mice was detected by using the same detection method as in Experimental Example 3. The conjugate numbers corresponding to each test group and control group are shown in Table 9. Table 9 Inhibition rate of hCFB protein in mice Table 9 shows the inhibition rate of hCFB protein in mice after administration of the siRNA conjugate of the present disclosure at a dose of 1 mg / kg. The results show that, compared with the reference conjugate 1, the conjugate 44 provided by the present disclosure has a significantly higher inhibition rate on CFB protein in hCFB transgenic mice within the experimental period of 43 days, even at a lower administration dose (1 mg / kg), especially at day 43, the reference conjugate 1 has no inhibition activity on CFB protein in hCFB transgenic mice, while the inhibition rate of conjugate 44 on CFB protein in hCFB transgenic mice can still reach 39.1% at day 43. This indicates that the conjugate provided by the present disclosure has long-acting inhibition on CFB protein in hCFB transgenic mice. Experimental Example 7 CFB mRNA inhibition activity of siRNA conjugate of the present disclosure in vitro This experimental example investigates the CFB mRNA inhibition activity of siRNA conjugates 34-39 of the present disclosure in hCFB transgenic mouse primary hepatocytes in vitro at concentrations of 5 nM and 0.5 nM. The same method as in Experimental Example 1 was used for cell culture, transfection of the conjugate, and RNA extraction and relative quantification of CFB mRNA, except that the conjugates used were conjugate 34, conjugate 35, conjugate 36, conjugate 37, conjugate 38 and conjugate 39, respectively. The results are shown in Table 10 below. Table 10 Inhibition activity of conjugates in hCFB transgenic mouse primary hepatocytes at different concentrations Table 10 shows the inhibition rate of CFB mRNA in hCFB transgenic mouse primary hepatocytes in vitro after transfection of siRNA conjugates of the present disclosure at 5 nM and 0.5 nM. The results show that the siRNA conjugates of the present disclosure exhibit excellent CFB mRNA inhibition capacity: the inhibition rate is 96.6%-97.9% at a concentration of 5 nM, and remains at a high inhibition rate of 95.3%-97.1% at a low concentration of 0.5 nM, indicating that the conjugates provided by the present disclosure have high and stable CFB mRNA inhibition activity. Experimental Example 8 Inhibitory activity of conjugates in HepG2 human hepatoma cells in vitro This experimental example investigates the inhibitory activity of conjugates 27-32 on CFB mRNA in HepG2 human hepatoma cells in vitro. The specific steps are as follows: [1] Cell culture HepG2 human hepatoma cells (purchased from Nanjing Keye Biotechnology Co., Ltd.) were cultured in a 37°C incubator containing 5% CO2 / 95% air using DMEM medium (MACGENE Co., Ltd.) added with 10% fetal bovine serum (FBS, RMBIO Co., Ltd.). HepG2 cells were seeded in 24-well plates at a density of 5x10 4 Cells were seeded in 24-well plates at a density of 5x10 TM Cells were seeded in 24-well plates at a density of 5x10 [2] Transfection For each siRNA conjugate to be tested, a working solution of the conjugate was prepared in PBS at a concentration of 20 μM and 0.2 μM (based on the amount of siRNA in the conjugate). The siRNA conjugates to be tested used were conjugate 27, conjugate 28, conjugate 29, conjugate 30, conjugate 31 and conjugate 32, respectively. For each siRNA conjugate, an 8A solution was prepared, each 8A solution containing 1.5 μL of the working solution of the conjugate at a concentration of 20 μM and 48.5 μL of cell maintenance medium. For each siRNA conjugate, an 8B solution was prepared, each 8B solution containing 1.5 μL of the working solution of the conjugate at a concentration of 0.2 μM and 48.5 μL of cell maintenance medium. An 8C solution was prepared, each 8C solution containing 1 μL of Lipofectamine TM RNAiMAX (Invitrogen Co., Ltd.) and 49 μL of Opti-MEM medium. For each conjugate, one 8A solution and one 8C solution were mixed to obtain a transfection complex 8X a in the culture wells, respectively, to obtain a transfection mixture containing the siRNA conjugate, denoted as test group 8X a , mixed evenly, the amount added being 100 μL / well, to obtain a transfection mixture at a concentration of 50 nM (based on the amount of siRNA). Two culture wells were transfected with the transfection complex 8X a containing the siRNA conjugate, respectively, denoted as test group 8X a1 -8X a6 . For each conjugate, one portion of the 8B solution and one portion of the 8C solution were mixed to obtain the transfection complex 8X b In the culture wells, the transfection complex 8X of each siRNA conjugate was added respectively b , mixed evenly, and the amount added was 100 μL / well to obtain a transfection mixture with a concentration of 0.5 nM (calculated as the amount of siRNA). The transfection complex 8X of each siRNA conjugate was added respectively to two culture wells to obtain a transfection mixture containing the siRNA conjugate, which was recorded as the test group 8X b The transfection complex 8X of each siRNA conjugate was added respectively to two culture wells to obtain a transfection mixture containing the siRNA conjugate, which was recorded as the test group 8X b1 -8X b6 One portion of the 8C solution was mixed with 50 μL of cell maintenance medium to obtain a blank transfection mixture. In another 4 culture wells, the blank transfection mixture was added respectively, and the amount added was 100 μL / well to obtain a transfection mixture without the siRNA conjugate, which was recorded as the blank control group. After 4 hours, 1 mL of DMEM medium added with 10% fetal bovine serum was supplemented to each well. The 24-well plate was placed in a CO2incubator for continuous culture for 24 hours. [3] Detection The total RNA in each well was extracted and reverse transcribed, and the relative quantification of the target gene CFB mRNA in each test group was calculated by using the same method as in Experimental Example 1. The results are shown in Table 11. Table 11 Inhibition rate of each conjugate on the target gene CFB mRNA Table 11 shows the relative inhibition rate of CFB mRNA in the in vitro HepG2 cells after transfection of 50 nM and 0.5 nM of the siRNA conjugate of the present disclosure. The results show that the inhibition rate of the siRNA conjugate provided by the present disclosure on CFB mRNA is above 79% at a concentration of 50 nM, and can even reach 85.4%, and the inhibition rate of the conjugate on CFB mRNA is above 68.3% at a concentration of 0.5 nM, and can even reach 78.3%. It is shown that the conjugate provided by the present disclosure has excellent inhibition activity on CFB mRNA. Experimental Example 9 Inhibition activity of the conjugate in monkey liver primary cells This experimental example investigates the inhibition activity of the conjugates 27-32 on CFB mRNA in the in vitro monkey liver primary cells. The specific steps are as follows: [1] Cell culture ​Monkey primary liver cells (purchased from Miaoshun (Shanghai) Biotechnology Co., Ltd.) were resuscitated using resuscitation medium (TPCS, catalog number HTS-R-120). After centrifugation, hepatocyte maintenance medium (TPCS, catalog number HNM-R-120) and hepatocyte plating medium (TPCS, catalog number HPM-R-120) were mixed at a volume ratio of 7:3 to prepare a mixed medium. The resuscitated monkey primary liver cells were thoroughly resuspended in this mixed medium. Primary monkey liver cells were cultured at a rate of 1×10⁻⁶. 5 The cells were seeded in 12-well plates, with two replicates for each sample. 1 mL of cell culture was added to each well. After 24 h of incubation, the culture medium was aspirated from the wells, and 1 mL of Opti-MEM medium (GIBCO, catalog number 31985-070) was added to each well. The plates were then incubated at 37°C in a 5% CO2 / 95% air incubator for 1.5 h. [2] Transfection For each siRNA conjugate to be tested, working solutions of the conjugate were prepared with PBS at concentrations of 2 μM and 0.2 μM (based on the amount of siRNA in the conjugate). The siRNA conjugates used were conjugate 27, conjugate 28, conjugate 29, conjugate 30, conjugate 31, and conjugate 32. For each siRNA conjugate, prepare a 9A solution, each containing 3 μL of 2 μM working solution of the conjugate and 97 μL of cell maintenance medium. For each siRNA conjugate, prepare a 9B solution, each containing 3 μL of 0.2 μM working solution of the conjugate and 97 μL of cell maintenance medium. Prepare 9C solutions, each containing 2 μL of Lipofectamine. TM 2000 (Invitrogen) and 98 μL Opti-MEM medium. For each conjugate, one part of solution 9A and one part of solution 9C were mixed to obtain transfection complex 9X. a In the culture wells (all containing primary monkey liver cells and Opti-MEM as described above), 9X of the transfection complex for each siRNA conjugate was added. a Mix thoroughly and add 200 μL per well to obtain a transfection mixture with a concentration of 5 nM (based on the amount of siRNA). Transfect two wells with each siRNA conjugate to obtain a transfection mixture containing the siRNA conjugate, denoted as test group 9X. a1 -9X a6 . For each conjugate, one portion of the 9B solution and one portion of the 9C solution were mixed to obtain the transfection complex 9X b In the culture wells, the transfection complex 9X of each siRNA conjugate was added respectively b , mixed evenly, and the amount added was 200 μL / well to obtain a transfection mixture with a concentration of 0.5 nM (calculated by the amount of siRNA). The transfection complex 9X of each siRNA conjugate was added respectively to two culture wells to obtain a transfection mixture containing the siRNA conjugate, which was recorded as the test group 9X b The transfection complex 9X of each siRNA conjugate was added respectively to two culture wells to obtain a transfection mixture containing the siRNA conjugate, which was recorded as the test group 9X b1 -9X b6 . One portion of the 9C solution was mixed with 100 μL of cell maintenance medium to obtain a blank transfection mixture. In another 4 culture wells, the blank transfection mixture was added respectively, and the amount added was 200 μL / well to obtain a transfection mixture without the siRNA conjugate, which was recorded as the blank control group. After 4 hours, 1 mL of hepatocyte maintenance medium was added to each well. The 12-well plate was placed in a CO2incubator for continuous culture for 24 hours. [3] Detection According to the method in Experimental Example 1, the expression level of the target gene CFB mRNA in each test group was calculated for relative quantification. The difference is that the PCR primer sequences for amplifying the target gene CFB and the internal reference gene GAPDH are shown in Table 12. Table 12 Primer sequence information The experimental results are shown in Table 13 below. Table 13 Inhibition rate of each conjugate on the target gene CFB mRNA Table 13 shows the relative inhibition rate of CFB mRNA in monkey primary cells in vitro after transfection of 5 nM and 0.5 nM of the siRNA conjugate of the present disclosure. The results show that the siRNA conjugate provided by the present disclosure has an inhibition rate of more than 90% even at a low concentration of 0.5 nM, and has excellent in vitro inhibition activity. The above describes some embodiments of the present disclosure in detail, but the present disclosure is not limited to the specific details in the above embodiments. Within the technical concept range of the present disclosure, various simple modifications can be made to the technical solutions of the present disclosure, and these simple modifications all belong to the protection range of the present disclosure. In addition, it should be noted that each specific technical feature described in the above some embodiments can be combined by any appropriate method without contradiction. In order to avoid unnecessary repetition, the present disclosure will not further describe various possible combination methods. Furthermore, the various embodiments of the present disclosure can be arbitrarily combined with each other unless they contradict each other, and it should be understood that the same should be construed as being included in the disclosure of the present disclosure.

Claims

1. A single-stranded oligonucleotide of 16-30 nucleotides in length having sufficient complementarity to a CFB mRNA to mediate an RNAi effect; each nucleotide in the single-stranded oligonucleotide is a modified or unmodified nucleotide, wherein, In the single-stranded oligonucleotide, at least one nucleotide is a nucleotide X, and at least one nucleotide is a fluorine-modified nucleotide; and, in the direction from the 5' end to the 3' end, at least one nucleotide X is located after the 8th nucleotide of the single-stranded oligonucleotide and is spaced 4-7 nucleotides apart from the 8th nucleotide; And, in the direction from the 5' end to the 3' end, if the 14th nucleotide of the single-stranded oligonucleotide is a nucleotide X, and all the nucleotides after the 15th nucleotide of the single-stranded oligonucleotide are modified nucleotides, then the 13th nucleotide of the single-stranded oligonucleotide is selected from one of an alkoxy-modified nucleotide, an alkyl-modified nucleotide, a substituted alkyl-modified nucleotide, an amine-modified nucleotide, a thermally unstable nucleotide and a BNA; Each nucleotide X is a deoxynucleotide or an unmodified nucleotide.

2. The single stranded oligonucleotide of claim 1, wherein, The length of the single-stranded oligonucleotide is 17-28, 19-26, or 20-24 nucleotides; or the length of the single-stranded oligonucleotide is 19, 21 or 23 nucleotides.

3. The single stranded oligonucleotide of claim 1 or 2, wherein, The number of nucleotides X is 1-3.

4. The single stranded oligonucleotide of any one of claims 1-3, wherein, Each nucleotide X is located after the 8th nucleotide of the single-stranded oligonucleotide; and, in the direction from the 5' end to the 3' end, each nucleotide X is spaced 3, 5, 7 or 10 nucleotides apart from the 8th nucleotide of the single-stranded oligonucleotide; or one of the nucleotides X is spaced 5 nucleotides apart from the 8th nucleotide.

5. The single stranded oligonucleotide of claim 4, wherein, The single-stranded oligonucleotide contains only one nucleotide X, which is spaced 5 nucleotides apart from the 8th nucleotide of the single-stranded oligonucleotide in the direction from the 5' end to the 3' end; Or, the single-stranded oligonucleotide contains two nucleotides X, in which one nucleotide X is spaced 5 nucleotides apart from the 8th nucleotide of the single-stranded oligonucleotide, and the other nucleotide X is spaced 3, 7 or 10 nucleotides apart from the 8th nucleotide of the single-stranded oligonucleotide in the direction from the 5' end to the 3' end.

6. The single stranded oligonucleotide of any one of claims 1-5, wherein, The number of modified nucleotides accounts for more than 50%, more than 70% or more than 85% of the total number of nucleotides in the single-stranded oligonucleotide; or the number of unmodified nucleotides in the single-stranded oligonucleotide is not more than 5, not more than 4, not more than 3, not more than 2 or not more than 1; or each of the total nucleotides in the single-stranded oligonucleotide is independently a modified nucleotide.

7. The single stranded oligonucleotide of any one of claims 1-6, wherein, The number of fluorine-modified nucleotides is 2-7.

8. The single stranded oligonucleotide of claim 7, wherein, In the direction from the 5' end to the 3' end, the fluorine-modified nucleotides refer to 2-5 of the 2nd, 5th, 6th, 7th, 12th, 16th, 18th and 19th nucleotides of the single-stranded oligonucleotide; Or, in the direction from the 5' end to the 3' end, the fluorine-modified nucleotides refer to 1 or 2 of the 2nd and 12th nucleotides, 1 or 2 of the 5th-7th nucleotides, and 0-2 of the 16th-19th nucleotides.

9. The single stranded oligonucleotide of claim 8, wherein, The fluorine-modified nucleotides refer to the 2nd and 6th nucleotides; or the 2nd, 6th and 16th nucleotides; or the 2nd, 5th, 7th, 12th and 16th nucleotides; or the 2nd, 7th, 12th, 16th and 19th nucleotides; or the 2nd, 6th, 12th, 16th and 19th nucleotides in the single-stranded oligonucleotide in the direction from the 5' end to the 3' end.

10. The single stranded oligonucleotide of claim 9, wherein, Each modified nucleotide in the single-stranded oligonucleotide, except for the nucleotide X and the fluorine-modified nucleotides, is independently selected from one of an alkoxy-modified nucleotide, a substituted alkoxy-modified nucleotide, an alkyl-modified nucleotide, a substituted alkyl-modified nucleotide, an amine-modified nucleotide, a thermally unstable nucleotide and a BNA.

11. The single stranded oligonucleotide of claim 10, wherein, There is no thermally unstable nucleotide in the single-stranded oligonucleotide, or the number of thermally unstable nucleotides is 1 or 2; or each modified nucleotide in the single-stranded oligonucleotide, except for the nucleotide X, the fluorine-modified nucleotides and the thermally unstable nucleotides, is selected from an alkoxy-modified nucleotide or a substituted alkoxy-modified nucleotide.

12. The single stranded oligonucleotide of claim 11, wherein, The single-stranded oligonucleotide has a length of 19-23 nucleotides, and The 14th nucleotide is the nucleotide X, 2 of the 5th-7th nucleotides and the 19th nucleotide and the 2nd, 12th and 16th nucleotides are fluorine-modified nucleotides, the 3rd nucleotide is an alkoxy-modified nucleotide or a substituted alkoxy-modified nucleotide, the 5th nucleotide is an alkoxy-modified nucleotide or a substituted alkoxy-modified nucleotide when it is not a fluorine-modified nucleotide, and each of the remaining nucleotides in the single-stranded oligonucleotide is an alkoxy-modified nucleotide in the direction from the 5' end to the 3' end; or The 12th and 14th nucleotides are the nucleotide X, the 2nd, 7th and 16th nucleotides are fluorine-modified nucleotides, and the 3rd or 5th nucleotide is an alkoxy-modified nucleotide or a substituted alkoxy-modified nucleotide, and each of the remaining nucleotides in the single-stranded oligonucleotide is an alkoxy-modified nucleotide in the direction from the 5' end to the 3' end; or The 14th nucleotide and the 16th nucleotide are the nucleotide X, the 2nd and 6th nucleotides are fluorine-modified nucleotides, the 13th nucleotide is a substituted alkoxy-modified nucleotide or a BNA, and the 3rd or 5th nucleotide is an alkoxy-modified nucleotide or a substituted alkoxy-modified nucleotide in the direction from the 5' end to the 3' end; one of the 1st-2nd nucleotides in the single-stranded oligonucleotide is a thermally unstable nucleotide in the direction from the 3' end to the 5' end, and each of the remaining nucleotides in the single-stranded oligonucleotide is an alkoxy-modified nucleotide; or one of the 16th-19th nucleotides and the 14th nucleotide is a nucleotide X, the 2nd and 6th nucleotides are fluorinated nucleotides, the 16th nucleotide is a fluorinated nucleotide when the 16th nucleotide is not the nucleotide X, the 13th nucleotide is a substituted alkoxy-modified nucleotide or a BNA, the 3rd or 5th nucleotide is an alkoxy-modified nucleotide or a substituted alkoxy-modified nucleotide; the 20th nucleotide is an alkoxy-modified nucleotide or a thermally unstable nucleotide; each of the remaining nucleotides in the single-stranded oligonucleotide is an alkoxy-modified nucleotide.

13. The single stranded oligonucleotide of claim 12, wherein, the single-stranded oligonucleotide has a length of 21 nucleotides, and in the 5' end to 3' end direction, the 14th nucleotide is a deoxynucleotide, the 2nd, 5th, 7th, 12th and 16th nucleotides are fluorinated nucleotides, the 3rd nucleotide is an alkoxy-modified nucleotide or a substituted alkoxy-modified nucleotide, and each of the remaining nucleotides in the single-stranded oligonucleotide is an alkoxy-modified nucleotide; or, in the 5' end to 3' end direction, the 14th nucleotide is a deoxynucleotide, the 2nd, 7th, 12th, 16th and 19th nucleotides are fluorinated nucleotides, and each of the remaining nucleotides in the single-stranded oligonucleotide is an alkoxy-modified nucleotide; or, in the 5' end to 3' end direction, the 14th nucleotide is a deoxynucleotide, the 2nd, 6th, 12th, 16th and 19th nucleotides are fluorinated nucleotides, and each of the remaining nucleotides in the single-stranded oligonucleotide is an alkoxy-modified nucleotide; or, in the 5' end to 3' end direction, the 12th and 14th nucleotides are deoxynucleotides, the 2nd, 7th and 16th nucleotides are fluorinated nucleotides, and each of the remaining nucleotides in the single-stranded oligonucleotide is an alkoxy-modified nucleotide; or, in the 5' end to 3' end direction, the 14th nucleotide is a deoxynucleotide, the 16th nucleotide is an unmodified nucleotide, the 2nd and 6th nucleotides are fluorinated nucleotides, the 13th nucleotide is a substituted alkoxy-modified nucleotide, in the 3' end to 5' end direction, the 2nd nucleotide of the single-stranded oligonucleotide is a thermally unstable nucleotide, and each of the remaining nucleotides in the single-stranded oligonucleotide is an alkoxy-modified nucleotide; or, in the 5' end to 3' end direction, the 14th nucleotide is a deoxynucleotide, the 19th nucleotide is an unmodified nucleotide, the 2nd, 6th and 16th nucleotides are fluorinated nucleotides, the 13th nucleotide is a substituted alkoxy-modified nucleotide, and each of the remaining nucleotides in the single-stranded oligonucleotide is an alkoxy-modified nucleotide.

14. The single stranded oligonucleotide of any one of claims 10-13, wherein, each alkoxy-modified nucleotide refers to a methoxy-modified nucleotide; and / or each substituted alkoxy-modified nucleotide refers to a 2'-O-methoxyethyl-modified nucleotide; and / or each BNA refers to a LNA or a cET BNA; and / or each thermally unstable nucleotide refers to a GNA. each alkoxy-modified nucleotide refers to a methoxy-modified nucleotide; and / or each substituted alkoxy-modified nucleotide refers to a 2'-O-methoxyethyl-modified nucleotide; and / or each BNA refers to a LNA or a cET BNA; and / or each thermally unstable nucleotide refers to a GNA.

15. The single stranded oligonucleotide of any one of claims 1-14, wherein, each of the at least 2 of the linking groups between adjacent nucleotides in the single stranded oligonucleotide is independently a phosphorothioate group with a modification group.

16. The single stranded oligonucleotide of claim 15, wherein, each of the 1-4 of the linking groups between adjacent nucleotides in the first 5 nucleotides from the 5' end and / or the 1-4 of the linking groups between adjacent nucleotides in the first 5 nucleotides from the 3' end of the single stranded oligonucleotide is independently a phosphorothioate group with a modification group; and / or if there are unmodified nucleotides in the single stranded oligonucleotide, each of the 1 or both of the 2 linking groups between each of the unmodified nucleotides and adjacent nucleotides is independently a phosphorothioate group with a modification group; and / or each of the 2-6, or 4, of the linking groups between adjacent nucleotides in the single stranded oligonucleotide is independently a phosphorothioate group with a modification group.

17. The single stranded oligonucleotide of claim 15 or 16, wherein, each of the linking groups between adjacent nucleotides in the first 3 nucleotides from the 5' end, the linking groups between adjacent nucleotides in the first 3 nucleotides from the 3' end of the single stranded oligonucleotide is independently a phosphorothioate group with a modification group; and / or if there are unmodified nucleotides in the single stranded oligonucleotide, each of the 1 or both of the 2 linking groups between each of the unmodified nucleotides and adjacent nucleotides is independently a phosphorothioate group with a modification group.

18. The single stranded oligonucleotide of any one of claims 15-17, wherein, Phosphonate groups having a modifying group are phosphorothioate groups having the structure of formula (28):

19. The single stranded oligonucleotide of any one of claims 1-18, wherein The 5'-terminal nucleotide of the single-stranded oligonucleotide is a 5'-hydroxyl nucleotide, a 5'-phosphate nucleotide, or a 5'-phosphate analog modified nucleotide, the 5'-hydroxyl nucleotide has a structure shown as formula (29); the 5'-phosphate nucleotide has a structure shown as formula (30); and the 5'-phosphate analog modified nucleotide has one selected from structures shown as formula (31) to formula (34): wherein R is selected from one of H, OH, OCH3, and F; Base represents a nucleic acid base selected from A, U, C, G, or T.

20. The single stranded oligonucleotide of any one of claims 1-19, wherein, the single stranded oligonucleotide has a length of 21 nucleotides, and in a direction from the 5' end to the 3' end, the 14th nucleotide is a deoxynucleotide, the 2nd, 5th, 7th, 12th, and 16th nucleotides are fluorine-modified nucleotides, the 3rd nucleotide is a methoxy-modified nucleotide, and each of the remaining nucleotides in the single stranded oligonucleotide is a methoxy-modified nucleotide; the linking groups between any two adjacent nucleotides in the first 1-3 nucleotides from the 5' end and the linking groups between any two adjacent nucleotides in the first 1-3 nucleotides from the 3' end are phosphorothioate groups; the 5' terminal nucleotide is a 5'-hydroxyl nucleotide represented by formula (29) or a 5'-vinylphosphonate-modified nucleotide represented by formula (31).

21. The single stranded oligonucleotide of any one of claims 1-20, wherein, the single stranded oligonucleotide is substantially or completely complementary to the CFB mRNA over a length of at least 16 nucleotides, or over a length of 16-25 nucleotides, or over a length of 18-23 nucleotides, or over a length of 19-21 nucleotides; and / or in a direction from the 5' end to the 3' end, the nucleotide sequence of the single stranded oligonucleotide except for the 1st nucleotide is completely complementary to the CFB mRNA; or, all of the nucleotides of the single stranded oligonucleotide are completely complementary to the CFB mRNA.

22. The single stranded oligonucleotide of any one of claims 1-21, wherein, the single stranded oligonucleotide contains a nucleotide sequence II, which is one selected from the following i)-iv): each of the at least 2 of the linking groups between adjacent nucleotides in the single stranded oligonucleotide is independently a phosphorothioate group with a modification group. each of the 1-4 of the linking groups between adjacent nucleotides in the first 5 nucleotides from the 5' end and / or the 1-4 of the linking groups between adjacent nucleotides in the first 5 nucleotides from the 3' end of the single stranded oligonucleotide is independently a phosphorothioate group with a modification group; and / or if there are unmodified nucleotides in the single stranded oligonucleotide, each of the 1 or both of the 2 linking groups between each of the unmodified nucleotides and adjacent nucleotides is independently a phosphorothioate group with a modification group; and / or each of the 2-6, or 4, of the linking groups between adjacent nucleotides in the single stranded oligonucleotide is independently a phosphorothioate group with a modification group. each of the linking groups between adjacent nucleotides in the first 3 nucleotides from the 5' end, the linking groups between adjacent nucleotides in the first 3 nucleotides from the 3' end of the single stranded oligonucleotide is independently a phosphorothioate group with a modification group; and / or if there are unmodified nucleotides in the single stranded oligonucleotide, each of the 1 or both of the 2 linking groups between each of the unmodified nucleotides and adjacent nucleotides is independently a phosphorothioate group with a modification group.

19. The single stranded oligonucleotide of any one of claims 1-18, wherein R is selected from one of H, OH, OCH3, and F; Base represents a nucleic acid base selected from A, U, C, G, or T. the single stranded oligonucleotide has a length of 21 nucleotides, and in a direction from the 5' end to the 3' end, the 14th nucleotide is a deoxynucleotide, the 2nd, 5th, 7th, 12th, and 16th nucleotides are fluorine-modified nucleotides, the 3rd nucleotide is a methoxy-modified nucleotide, and each of the remaining nucleotides in the single stranded oligonucleotide is a methoxy-modified nucleotide; the linking groups between any two adjacent nucleotides in the first 1-3 nucleotides from the 5' end and the linking groups between any two adjacent nucleotides in the first 1-3 nucleotides from the 3' end are phosphorothioate groups; the 5' terminal nucleotide is a 5'-hydroxyl nucleotide represented by formula (29) or a 5'-vinylphosphonate-modified nucleotide represented by formula (31). the single stranded oligonucleotide is substantially or completely complementary to the CFB mRNA over a length of at least 16 nucleotides, or over a length of 16-25 nucleotides, or over a length of 18-23 nucleotides, or over a length of 19-21 nucleotides; and / or in a direction from the 5' end to the 3' end, the nucleotide sequence of the single stranded oligonucleotide except for the 1st nucleotide is completely complementary to the CFB mRNA; or, all of the nucleotides of the single stranded oligonucleotide are completely complementary to the CFB mRNA. the single stranded oligonucleotide contains a nucleotide sequence II, which is one selected from the following i)-iv): i) the nucleotide sequence II is equal in length to the nucleotide sequence set forth in SEQ ID NO: 2, and differs in no more than 3 bases from the nucleotide sequence set forth in SEQ ID NO: 2: 5'-Z2GACAUCCAGAUAAUCCUC-3' (SEQ ID NO: 2), wherein Z2 is A or U, the nucleotide sequence II comprises a nucleotide Z'2 at a position corresponding to Z2, Z'2 being the first nucleotide at the 5' end of the single-stranded oligonucleotide sequence; ii) the nucleotide sequence II is equal in length to the nucleotide sequence set forth in SEQ ID NO: 4, and differs in no more than 3 bases from the nucleotide sequence set forth in SEQ ID NO: 4: 5'-Z4UCCAGAUAAUCCUCCCUU-3' (SEQ ID NO: 4), wherein Z4 is A or U, the nucleotide sequence II comprises a nucleotide Z'4 at a position corresponding to Z4, Z'4 being the first nucleotide at the 5' end of the single-stranded oligonucleotide sequence; iii) the nucleotide sequence II is equal in length to the nucleotide sequence set forth in SEQ ID NO: 6, and differs in no more than 3 bases from the nucleotide sequence set forth in SEQ ID NO: 6: 5'-Z6UCACUCACAUUGUAGUAG-3' (SEQ ID NO: 6), wherein Z6 is A or U, the nucleotide sequence II comprises a nucleotide Z'6 at a position corresponding to Z6, Z'6 being the first nucleotide at the 5' end of the single-stranded oligonucleotide sequence; iv) the nucleotide sequence II is equal in length to the nucleotide sequence set forth in SEQ ID NO: 8, and differs in no more than 3 bases from the nucleotide sequence set forth in SEQ ID NO: 8: 5'-Z8GUGGAAAGAGAUCUCAUC-3' (SEQ ID NO: 8), wherein Z8 is A or U, the nucleotide sequence II comprises a nucleotide Z'8 at a position corresponding to Z8, Z'8 being the first nucleotide at the 5' end of the single-stranded oligonucleotide sequence; v) the nucleotide sequence II is equal in length to the nucleotide sequence set forth in SEQ ID NO: 74, and differs in no more than 3 bases from the nucleotide sequence set forth in SEQ ID NO: 74: 5'-Z 10 UGAUGUAGACCUCCUUCC-3' (SEQ ID NO: 74), or 5'-Z 10 5'-Z 10 UGAUGUAGACCUCC Among them, Z 10 For A or U, the nucleotide sequence II contains a position corresponding to Z. 10 nucleotide Z' 10 The Z' 10 It is the first nucleotide at the 5' end of the single-stranded oligonucleotide sequence; vi) the nucleotide sequence II is equal in length to the nucleotide sequence set forth in SEQ ID NO: 76, and differs in no more than 3 bases from the nucleotide sequence set forth in SEQ ID NO: 76: 5'-Z 12 UGAUGUGAAAGUCUCGGG-3' (SEQ ID NO: 76), Among them, Z 12 For A or U, the nucleotide sequence II contains a position corresponding to Z. 12 nucleotide Z' 12 The Z' 12 It is the first nucleotide at the 5' end of the single-stranded oligonucleotide sequence.

23. The single stranded oligonucleotide of claim 22, wherein, the nucleotide sequence II differs in no more than 1 base from the nucleotide sequence set forth in SEQ ID NO: 2; or the nucleotide sequence II differs in no more than 1 base from the nucleotide sequence set forth in SEQ ID NO: 4; or the nucleotide sequence II differs in no more than 1 base from the nucleotide sequence set forth in SEQ ID NO: 6; or the nucleotide sequence II differs in no more than 1 base from the nucleotide sequence set forth in SEQ ID NO: 8; or the nucleotide sequence II differs in no more than 1 base from the nucleotide sequence set forth in SEQ ID NO: 74; or the nucleotide sequence II differs in no more than 1 base from the nucleotide sequence set forth in SEQ ID NO: 76; or there is no base difference between the nucleotide sequence II and the nucleotide sequence shown in SEQ ID NO: 2; or there is no base difference between the nucleotide sequence II and the nucleotide sequence shown in SEQ ID NO: 4; or there is no base difference between the nucleotide sequence II and the nucleotide sequence shown in SEQ ID NO: 6; or there is no base difference between the nucleotide sequence II and the nucleotide sequence shown in SEQ ID NO: 8; or there is no base difference between the nucleotide sequence II and the nucleotide sequence shown in SEQ ID NO: 74; or there is no base difference between the nucleotide sequence II and the nucleotide sequence shown in SEQ ID NO:

76.

24. The single stranded oligonucleotide of claim 22 or 23, wherein, The single-stranded oligonucleotide further comprises a nucleotide sequence IV, which is linked to the 3' end of the nucleotide sequence II, has a length of 1, 2, 3 or 4 nucleotides, each nucleotide in the nucleotide sequence IV is independently one of non-fluorinated modified nucleotides, the nucleotide sequence IV is substantially reverse complementary or completely reverse complementary to CFB mRNA, each of the non-fluorinated modified nucleotides is independently selected from one of 2'-methoxy modified nucleotides, 2'-alkyl modified nucleotides with an alkyl group having a carbon number of 1-3, 2'-amino modified nucleotides, 2'-substituted amino modified nucleotides and heat unstable nucleotides; or the length of the nucleotide sequence IV is 2 nucleotides.

25. The single stranded oligonucleotide of claim 22 or 24, wherein, The single-stranded oligonucleotide further comprises a nucleotide sequence V, each nucleotide in the nucleotide sequence V is independently a non-fluorinated modified nucleotide, the length of the nucleotide sequence V is 1-3 nucleotides, which is linked to the 3' end of the nucleotide sequence IV or the nucleotide sequence II; the single-stranded oligonucleotide forms a double-stranded oligonucleotide with the sense strand, the 3' overhanging end of the antisense strand of the double-stranded oligonucleotide is the nucleotide sequence V; or the length of the nucleotide sequence V is 2 nucleotides, and in the direction from the 5' end to the 3' end, the nucleotide sequence V is 2 consecutive thymine deoxynucleotides, 2 consecutive uracil nucleotides, or is completely reverse complementary to CFB mRNA; or the single-stranded oligonucleotide is the antisense strand of any one of siRNAa1, siRNAb1, siRNAc1, siRNAd1, siRNAe1 or siRNAf1 listed in Table 1; or the single-stranded oligonucleotide is the antisense strand of any one of conjugate 1-conjugate 44 listed in Table 2A.

26. A double stranded oligonucleotide comprising a sense strand and an antisense strand, each nucleotide in the sense strand being a modified or unmodified nucleotide, the sense strand and antisense strand being at least partially reverse complementary forming a double stranded region, wherein, The antisense strand is the single-stranded oligonucleotide according to any one of claims 1-25.

27. The double-stranded oligonucleotide of claim 26, wherein, The length of the sense strand is 19-21 nucleotides; or the length of the sense strand and the antisense strand is the same, and both are 19, 20 or 21 nucleotides; or the length of the sense strand is 19 nucleotides, and the length of the antisense strand is 20-24 nucleotides; or the length of the sense strand is 20 nucleotides, and the length of the antisense strand is 21-24 nucleotides; or the sense strand is 21 nucleotides in length and the antisense strand is 22-24 nucleotides in length; or the sense strand is 19 nucleotides in length and the antisense strand is 21 nucleotides in length; or the sense strand is 21 nucleotides in length and the antisense strand is 23 nucleotides in length.

28. The double-stranded oligonucleotide of any one of claims 26-27, wherein, 2-3 of the 11th-13thnucleotides from the 3' end to the 5' end of the sense strand are fluoro-modified nucleotides, the 1stnucleotide and / or the last nucleotide is an alkoxy-modified nucleotide or an inverted abasic deoxynucleotide, and the nucleotides at the remaining positions of the sense strand are non-fluoro-modified nucleotides, each of which is independently selected from one of an alkoxy-modified nucleotide, an alkyl-modified nucleotide, an amine-modified nucleotide, and a thermally unstable nucleotide.

29. The double-stranded oligonucleotide of claim 28, wherein, 2-3 of the 11th-13thnucleotides from the 3' end to the 5' end of the sense strand are fluoro-modified nucleotides, the 1stnucleotide and / or the last nucleotide is an alkoxy-modified nucleotide or an inverted abasic deoxynucleotide, and the nucleotides at the remaining positions of the sense strand are alkoxy-modified nucleotides.

30. The double-stranded oligonucleotide of claim 28 or 29, wherein, each of the alkoxy-modified nucleotides is a methoxy-modified nucleotide.

31. The double-stranded oligonucleotide of any one of claims 26-30, wherein, at least one of the linking groups connecting adjacent two nucleotides in the sense strand is a phosphate group with a modification group, which is present between two adjacent nucleotides from the 1stto the 5thnucleotide at the 5' end and between two adjacent nucleotides from the 1stto the 5thnucleotide at the 3' end of the sense strand.

32. The double-stranded oligonucleotide of claim 31, wherein, each of 1-4 of the linking groups between adjacent nucleotides from the 1stto the 5thnucleotide at the 5' end and / or 1-4 of the linking groups between adjacent nucleotides from the 1stto the 5thnucleotide at the 3' end of the sense strand is independently a phosphate group with a modification group; or each of the phosphate groups with a modification group is a phosphorothioate group with a structure as shown in formula (28); or the sense strand is the sense strand of any one of siRNAa1, siRNAb1, siRNAc1, siRNAd1, siRNAe1, or siRNAf1 listed in Table 1; or the sense strand is the sense strand of any one of conjugate 1-conjugate 44 listed in Table 2A.

33. The double-stranded oligonucleotide of any one of claims 26-32, wherein, the sense strand comprises 19-21 nucleotides and the antisense strand comprises 21-23 nucleotides; 2-3 of the 11th-13thnucleotides from the 3' end to the 5' end of the sense strand are fluoro-modified nucleotides, the 1stnucleotide and / or the last nucleotide is an alkoxy-modified nucleotide or an inverted abasic deoxynucleotide, and the nucleotides at the remaining positions of the sense strand are alkoxy-modified nucleotides. each of 1-4 of the linking groups between adjacent nucleotides of the first to fifth nucleotides from the 5' end of the sense strand, and / or 1-4 of the linking groups between adjacent nucleotides of the first to third nucleotides from the 3' end of the sense strand, is independently a phosphorothioate group with a modification group.

34. The double-stranded oligonucleotide of claim 33, wherein, the sense strand comprises 19-21 nucleotides, and the antisense strand comprises 21-23 nucleotides; in the sense strand, in the direction from the 3' end to the 5' end, the 11th and 13th nucleotides are fluorine-modified nucleotides, the 1st nucleotide is an inverted dealkylated deoxynucleotide, and the nucleotides at the remaining positions are alkoxy-modified nucleotides; 1-4 of the linking groups between adjacent nucleotides of the first to third nucleotides from the 5' end of the sense strand, and / or 1-4 of the linking groups between adjacent nucleotides of the first to third nucleotides from the 3' end of the sense strand, are phosphorothioate groups with a modification group; In the antisense strand, the 14th nucleotide is a deoxynucleotide, the 2nd, 5th, 7th, 12th and 16th nucleotides are fluorine-modified nucleotides, the 3rd nucleotide is an alkoxy-modified nucleotide or a substituted alkoxy-modified nucleotide, and each of the remaining nucleotides in the antisense strand is an alkoxy-modified nucleotide; or, in the antisense strand, the 14th nucleotide is a deoxynucleotide, the 2nd, 7th, 12th, 16th and 19th nucleotides are fluorine-modified nucleotides, and each of the remaining nucleotides in the antisense strand is an alkoxy-modified nucleotide; or, in the antisense strand, the 14th nucleotide is a deoxynucleotide, the 2nd, 6th, 12th, 16th and 19th nucleotides are fluorine-modified nucleotides, and each of the remaining nucleotides in the antisense strand is an alkoxy-modified nucleotide; or, in the antisense strand, the 12th and 14th nucleotides are deoxynucleotides, the 2nd, 7th and 16th nucleotides are fluorine-modified nucleotides, and each of the remaining nucleotides in the antisense strand is an alkoxy-modified nucleotide; or, in the antisense strand, the 14th nucleotide is a deoxynucleotide, the 16th nucleotide is an unmodified nucleotide, the 2nd and 6th nucleotides are fluorine-modified nucleotides, and the 13th nucleotide is a substituted alkoxy-modified nucleotide, the 2nd nucleotide from the 3' end is a thermally unstable nucleotide, and each of the remaining nucleotides in the antisense strand is an alkoxy-modified nucleotide; or, in the antisense strand, the 14th nucleotide is a deoxynucleotide, the 19th nucleotide is an unmodified nucleotide, the 2nd, 6th and 16th nucleotides are fluorine-modified nucleotides, and the 13th nucleotide is a substituted alkoxy-modified nucleotide, and each of the remaining nucleotides in the antisense strand is an alkoxy-modified nucleotide; the linkage between two adjacent nucleotides at the 1st-3rd nucleotides from the 5' end and the linkage between two adjacent nucleotides at the 1st-3rd nucleotides from the 3' end of the antisense strand are phosphoester groups with a modification group, and if there is an unmodified nucleotide, the linkage between each unmodified nucleotide and the adjacent nucleotide is a phosphoester group with a modification group; and the 5' terminal nucleotide of the antisense strand is a 5'-hydroxyl nucleotide represented by formula (29), a 5'-phosphate nucleotide represented by formula (30), or a 5'-vinyl phosphate-modified nucleotide represented by formula (31).

35. The double-stranded oligonucleotide of claim 34, wherein, The sense strand comprises 19 nucleotides, and the antisense strand comprises 21 nucleotides. In the sense strand, the 11th and 13th nucleotides from the 3' end to the 5' end are fluorine-modified nucleotides, the 1st nucleotide is an inverted de-alkylated deoxynucleotide, and the nucleotides at the remaining positions are methoxy-modified nucleotides; the linking group between the adjacent nucleotides at the 1st-3rd nucleotides at the 5' end of the sense strand is a phosphorothioate group; In the antisense strand, the 14th nucleotide from the 5' end to the 3' end is a deoxynucleotide, the 2nd, 5th, 7th, 12th and 16th nucleotides are fluorine-modified nucleotides, and each of the remaining nucleotides in the antisense strand is a methoxy-modified nucleotide; the linking group between the two adjacent nucleotides at the 1st-3rd nucleotides at the 5' end of the antisense strand and the linking group between the two adjacent nucleotides at the 1st-3rd nucleotides at the 3' end of the antisense strand are phosphorothioate groups; the 5' end nucleotide of the antisense strand is a 5'-hydroxyl nucleotide represented by formula (29) or a 5'-vinyl phosphate-modified nucleotide represented by formula (31).

36. The double-stranded oligonucleotide of any one of claims 26-35, wherein, The double-stranded region formed by the sense strand and the antisense strand contains 16-23 base pairs; or the double-stranded region formed by the sense strand and the antisense strand contains 18, 19, 20 or 21 base pairs; and / or the sense strand and the antisense strand are substantially reverse complementary or completely reverse complementary within the double-stranded region; And / or the number of base differences between the sense strand and the CFB mRNA is not more than 3, or not more than 2, or not more than 1; or there is no base difference between the sense strand and the CFB mRNA.

37. The double-stranded oligonucleotide of claim 35, wherein, The double-stranded oligonucleotide is an siRNA.

38. The double-stranded oligonucleotide of claim 37, wherein, The double-stranded oligonucleotide contains a sense strand and an antisense strand, the sense strand contains a nucleotide sequence I, and the antisense strand contains a nucleotide sequence II; the double-stranded oligonucleotide is selected from one group consisting of the following i)-iv) sequences: i) the nucleotide sequence I is equal in length to the nucleotide sequence represented by SEQ ID NO: 1 and has no more than 3 base differences, and the nucleotide sequence II is equal in length to the nucleotide sequence represented by SEQ ID NO: 2 and has no more than 3 base differences: 5'-GAGGAUUAUCUGGAUGUCZ1-3' (SEQ ID NO: 1) 5'-Z2GACAUCCAGAUAAUCCUC-3' (SEQ ID NO: 2); wherein Z1 is U, A or an inverted de-alkylated deoxynucleotide, Z2 is A or U, the nucleotide sequence I contains a nucleotide Z'1 corresponding to the position of Z1, the nucleotide sequence II contains a nucleotide Z'2 corresponding to the position of Z2, and Z'2 is the first nucleotide at the 5' end of the antisense strand; ii) the nucleotide sequence I is equal in length to the nucleotide sequence represented by SEQ ID NO: 3 and has no more than 3 base differences, and the nucleotide sequence II is equal in length to the nucleotide sequence represented by SEQ ID NO: 4 and has no more than 3 base differences: 5'-GAGGAUUAUCUGGAUGUCZ1-3' (SEQ ID NO: 1) 5'-Z2GACAUCCAGAUAAUCCUC-3' (SEQ ID NO: 2); wherein Z1 is U, A or an inverted de-alkylated deoxynucleotide, Z2 is A or U, the nucleotide sequence I contains a nucleotide Z'1 corresponding to the position of Z1, the nucleotide sequence II contains a nucleotide Z'2 corresponding to the position of Z2, and Z'2 is the first nucleotide at the 5' end of the antisense strand; 5'-AAGGGAGGAUUAUCUGGAZ3-3' (SEQ ID NO: 3) 5'-Z4UCCAGAUAAUCCUCCCUU-3' (SEQ ID NO: 4); wherein Z3 is U, A or an inverted abasic deoxynucleotide, Z4 is A or U, the nucleotide sequence I comprises a nucleotide Z'3 at a position corresponding to Z3, the nucleotide sequence II comprises a nucleotide Z'4 at a position corresponding to Z4, and Z'4 is the first nucleotide at the 5' end of the antisense strand; iii) the nucleotide sequence I is identical in length to the nucleotide sequence set forth in SEQ ID NO: 5 and differs by no more than 3 bases, and the nucleotide sequence II is identical in length to the nucleotide sequence set forth in SEQ ID NO: 6 and differs by no more than 3 bases: 5'-CUACUACAAUGUGAGUGAZ5-3' (SEQ ID NO: 5) 5'-Z6UCACUCACAUUGUAGUAG-3' (SEQ ID NO: 6); wherein Z5 is U, A or an inverted abasic deoxynucleotide, Z6 is A or U, the nucleotide sequence I comprises a nucleotide Z'5 at a position corresponding to Z5, the nucleotide sequence II comprises a nucleotide Z'6 at a position corresponding to Z6, and Z'6 is the first nucleotide at the 5' end of the antisense strand; iv) the nucleotide sequence I is identical in length to the nucleotide sequence set forth in SEQ ID NO: 7 and differs by no more than 3 bases, and the nucleotide sequence II is identical in length to the nucleotide sequence set forth in SEQ ID NO: 8 and differs by no more than 3 bases: 5'-GAUGAGAUCUCUUUCCACZ7-3' (SEQ ID NO: 7) 5'-Z8GUGGAAAGAGAUCUCAUC-3' (SEQ ID NO: 8); wherein Z7 is U, A or an inverted abasic deoxynucleotide, Z8 is A or U, the nucleotide sequence I comprises a nucleotide Z'7 at a position corresponding to Z7, the nucleotide sequence II comprises a nucleotide Z'8 at a position corresponding to Z8, and Z'8 is the first nucleotide at the 5' end of the antisense strand; v) the nucleotide sequence I is identical in length to the nucleotide sequence set forth in SEQ ID NO: 73 and differs by no more than 3 bases, and the nucleotide sequence II is identical in length to the nucleotide sequence set forth in SEQ ID NO: 74 and differs by no more than 3 bases: 5'-GGAAGGAGGUCUACAUCZ9-3' (SEQ ID NO: 73) 5'-Z 10 UGAUGUAGACCUCCUUCC-3' (SEQ ID NO: 74); and 5'-Z 10 GGAGGUUCCCGAGAUGUUUCUUA-3' (SEQ ID Where Z9 is U, A, or reverse debased deoxynucleotide, Z 10 For A or U, nucleotide sequence I contains nucleotide Z'9 at position Z9, and nucleotide sequence II contains nucleotide Z at position Z. 10 nucleotide Z' 10 The Z' 10 It is the first nucleotide at the 5' end of the antisense strand; vi) the nucleotide sequence I is identical in length to the nucleotide sequence set forth in SEQ ID NO: 75 and differs by no more than 3 bases, and the nucleotide sequence II is identical in length to the nucleotide sequence set forth in SEQ ID NO: 76 and differs by no more than 3 bases: 5'-CCCGAGACUUUCACAUCAZ 11 -3'(SEQ ID NO:75) 5'-Z 12 UGAUGUGAAAGUCUCGGG-3' (SEQ ID NO: 76); wherein Z is U, A or an inverted abasic deoxynucleotide, 11 A or U, the nucleotide sequence I comprising a nucleotide Z' at a position corresponding to Z, 12 11 11 12 12 12 is the first nucleotide at the 5' end of the antisense strand.​​​​​ 39. The double-stranded oligonucleotide of claim 38, wherein, the nucleotide sequence I is not more than 1 base different from the nucleotide sequence set forth in SEQ ID NO: 1, 3, 5, 7, 73 or 75, and the nucleotide sequence II is not more than 1 base different from the nucleotide sequence set forth in SEQ ID NO: 2, 4, 6, 8, 74 or 76.

40. The double-stranded oligonucleotide of claim 39, wherein, the double-stranded oligonucleotide is the double-stranded oligonucleotide set forth in any one of siRNAa1, siRNAb1, siRNAc1, siRNAd1, siRNAe1 or siRNAf1 listed in Table 1.

41. An oligonucleotide conjugate comprising an oligonucleotide group and a delivery group conjugated to the oligonucleotide group, the oligonucleotide group independently being a group formed by removing one or more atoms or atom groups from the single-stranded oligonucleotide according to any one of claims 1-25 or the double-stranded oligonucleotide according to any one of claims 26-40.

42. The oligonucleotide conjugate of claim 41, wherein, the delivery group comprises a linker group and a pharmaceutically acceptable targeting group, and the oligonucleotide group, the linker group and the targeting group are covalently or non-covalently linked in sequence, each of the targeting groups being selected from a ligand capable of binding to a cell surface receptor or a group capable of increasing the compatibility with a tissue; alternatively, the oligonucleotide conjugate comprises an oligonucleotide group formed by siRNA listed in Table 1; Alternatively, the oligonucleotide conjugate has the structure shown in Formula (403) in formula (403), Nu is an oligonucleotide group; or the oligonucleotide group is a double-stranded oligonucleotide group, and the P atom is covalently linked to the 3' terminal nucleotide of the sense strand of the double-stranded oligonucleotide group; or the 3' terminal of the sense strand of the double-stranded oligonucleotide group is a reverse deoxy-debase nucleotide, and the P atom is covalently linked to the double-stranded oligonucleotide group by replacing the hydrogen atom in the hydroxyl group via a methylene group to the ribose ring in the reverse deoxy-debase nucleotide of the 3' terminal of the sense strand of the double-stranded oligonucleotide group; alternatively, the oligonucleotide conjugate is one of conjugates 1-conjugate 44 listed in Table 2A.

43. A pharmaceutically acceptable salt of the single-stranded oligonucleotide according to any one of claims 1-25, the double-stranded oligonucleotide according to any one of claims 26-40 or the oligonucleotide conjugate according to claim 41 or 42; alternatively, the pharmaceutically acceptable salt is a water-soluble salt of part or all of the single-stranded oligonucleotide, the double-stranded oligonucleotide or the oligonucleotide conjugate; alternatively, the water-soluble salt is one or more of an amine salt, an alkali metal salt and an alkaline earth metal salt; alternatively, the amine salt is one or more of an ammonium salt, a methylamine salt, a tertiary amine salt, a quaternary ammonium salt, the alkali metal salt is one or more of a potassium salt or a sodium salt, and the alkaline earth metal salt is one or more of a calcium salt or a magnesium salt; alternatively, the tertiary amine salt is a triethylamine salt, a triisopropylamine salt, a N,N-diisopropylethylamine salt; alternatively, the pharmaceutically acceptable salt is a sodium salt or a partial sodium salt of the single-stranded oligonucleotide, the double-stranded oligonucleotide or the oligonucleotide conjugate.

44. A pharmaceutical composition comprising one or more of the single-stranded oligonucleotide of any one of claims 1-25, the double-stranded oligonucleotide of any one of claims 26-40, the oligonucleotide conjugate of claim 41 or 42, and the pharmaceutically acceptable salt of claim 43, and a pharmaceutically acceptable excipient; or the pharmaceutically acceptable excipient is one or more of a solvent, a protective agent, an osmotic pressure regulator, and a pharmaceutically acceptable other carrier; or the solvent is one of deionized water, water for injection, a pH buffer, physiological saline, ethanol, or an aqueous ethanol solution.

45. Use of one or more of the single-stranded oligonucleotide of any one of claims 1-25, the double-stranded oligonucleotide of any one of claims 26-40, the oligonucleotide conjugate of claim 41 or 42, the pharmaceutically acceptable salt of claim 43, and the pharmaceutical composition of claim 44 in the manufacture of a medicament for treating and / or preventing a disease or condition associated with CFB mRNA level.

46. The use of claim 45, wherein, the disease or condition associated with CFB mRNA level is selected from one or more of primary membranous nephropathy, hemolytic uremic syndrome, C3 glomerulopathy, IgA nephropathy, diabetic nephropathy, polycystic kidney disease, membranous nephropathy, paroxysmal nocturnal hemoglobinuria (PNH), myasthenia gravis (MG), age-related macular degeneration, an ophthalmic disease, and rheumatoid arthritis; or the disease or condition associated with CFB mRNA level is selected from one or more of C3 glomerulopathy, myasthenia gravis (MG), IgA nephropathy, diabetic nephropathy, and polycystic kidney disease.

47. A method of treating and / or preventing a disease or condition associated with CFB mRNA level, the method comprising administering to a subject in need thereof an effective amount of one or more of the single-stranded oligonucleotide of any one of claims 1-25, the double-stranded oligonucleotide of any one of claims 26-40, the oligonucleotide conjugate of claim 41 or 42, the pharmaceutically acceptable salt of claim 43, and the pharmaceutical composition of claim 44.

48. A method of modulating CFB mRNA expression level in a cell, the method comprising contacting the cell with an effective amount of one or more of the single-stranded oligonucleotide of any one of claims 1-25, the double-stranded oligonucleotide of any one of claims 26-40, the oligonucleotide conjugate of claim 41 or 42, the pharmaceutically acceptable salt of claim 43, and the pharmaceutical composition of claim 44.

49. One or more of the single-stranded oligonucleotide of any one of claims 1-25, the double-stranded oligonucleotide of any one of claims 26-40, the oligonucleotide conjugate of claim 41 or 42, the pharmaceutically acceptable salt of claim 43, and the pharmaceutical composition of claim 44 for use as a medicament.

50. A cell expressing CFB mRNA, the cell comprising one or more of the single- stranded oligonucleotide of any one of claims 1-25, the double-stranded oligonucleotide of any one of claims 26-40, the oligonucleotide conjugate of claim 41 or 42, the pharmaceutically acceptable salt of claim 43, and the pharmaceutical composition of claim 44.

51. A kit comprising one or more of the single-stranded oligonucleotide of any one of claims 1-25, the double-stranded oligonucleotide of any one of claims 26-40, the oligonucleotide conjugate of claim 41 or 42, the pharmaceutically acceptable salt of claim 43, and the pharmaceutical composition of claim 44.

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