82 results about "Anti sense" patented technology

Provided is a circular multimeric tandem RNA sense strand, comprising at least one sense strand sequence and at least one spacer sequence. The circular RNA is derived from an engineered parental DNA template containing all essential sequences, and sequentially comprises a first cyclization element, optionally at least one first restriction enzyme recognition sequence, at least one target sequence, optionally at least one second restriction enzyme recognition sequence, and a second cyclization element. The circular multimeric tandem RNA sense strand can bind and deliver a plurality of antisense strand RNA, increasing the binding of the sense strand and the antisense strand while utilizing the stability advantage of circular RNA.

The invention provides annular multi-tandem PCSK9 siRNA, which comprises at least one positive-sense strand sequence and at least one spacer sequence. The sense strand of the cyclic siRNA is derived from an engineered parent DNA template containing all essential sequences, comprising in the following order a first cyclization element, optionally at least one first restriction enzyme recognition sequence, at least one target sequence, optionally at least one second restriction enzyme recognition sequence, and a second cyclization element. The annular multi-tandem RNA positive-sense strand can combine and deliver a plurality of antisense strand RNAs, and the combination of the positive-sense strand and the antisense strand is increased while the stability advantage of the annular RNA is utilized.

The present invention relates to a nucleic acid molecule inhibiting factor 11 (FXI) gene expression in a cell by means of RNAi, comprising a sense sequence and an antisense sequence complementary to each other, or consisting of a sense sequence and an antisense sequence complementary to each other. The FXI inhibition rate of the nucleic acid molecule is significantly superior to that of other small nucleic acid molecules which inhibit the expression of FXI by means of RNAi.

Provided is a circular concatemeric PCSK9 siRNA, comprising at least one sense strand sequence and at least one spacer sequence. The sense strand of the circular siRNA is derived from an engineered parental DNA template containing all essential sequences, which comprises, in the following order: a first cyclization element, optionally at least one first restriction enzyme recognition sequence, at least one target sequence, optionally at least one second restriction enzyme recognition sequence, and a second cyclization element. The sense strand of the circular concatemeric RNA can bind and deliver a plurality of antisense strand RNAs, enhancing the binding between the sense and antisense strands while leveraging the stability advantage of the circular RNA.

The invention discloses siRNA (small interfering Ribonucleic Acid) targeting TMEM86A and application thereof, and relates to the technical field of biology, the siRNA comprises the following positive-sense strands and antisense strands: siRNA-001: a positive-sense strand: 5 '-GAAGAGCGAAGGACCCAAATT-3'; according to the tumor-associated macrophage, TMEM86A has a positive-sense strand of 5 '-TTTGGGTCCTTCGCTTCT-3', an antisense strand of 5 '-TTTGGGTCCTGTCGCTTCT-3', siRNA-002 has a positive-sense strand of 5 '-GGCTCATGGTTCGGTTTT-3', and an antisense strand of 5 '-AAACCGAACCCATGAGCCT-3'. According to the tumor-associated macrophage, single cell sequencing analysis finds that TMEM86A is highly expressed in tumor-associated macrophages, and the development of tumors is inhibited by designing siRNA of TMEM86A to target the tumor-associated macrophages in a colon cancer tumor microenvironment.

The invention generally relates to capturing, amplifying, and sequencing nucleic acids. In certain embodiments, copies of the sense and antisense strands of a duplex template nucleic acid are captured using linked capture probes and multiple binding and extension steps to improve specificity over traditional single binding target capture techniques. Methods of seeding sequencing clusters with sense and antisense strands of a target nucleic acid are also disclosed including identifying the strands using sense-specific barcodes and confirming base calls using two sense-specific sequencing reads. Linked adapters may be used to increase adapter ligation selectively or efficiency and yield.

This invention discloses five RNAi molecules targeting the genome of the small cutworm, all of which are double-stranded RNA molecules composed of a sense strand and a complementary antisense strand, wherein the nucleotide sequence of the sense strand is selected from SEQ ID NOs:1-5. The lethality of these RNAi molecules against the small cutworm is all above 80%.

Double-stranded ribonucleic acid (dsRNAi) agents that target exon 1 of the huntingtin (HTT) gene are provided.SOLUTION: A double-stranded ribonucleic acid (dsRNA) agent for inhibiting the expression of huntingtin (HTT), the agent comprising a sense strand and an antisense strand forming a double-stranded region, wherein the sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from a certain specific nucleotide sequence, and the antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from another certain specific nucleotide sequence, provided are dsRNA agents wherein one or more lipophilic moieties are conjugated to one or more internal positions on at least one of the sense or antisense strands.SELECTED DRAWING: None

The present application relates to a nucleic acid molecule inhibiting ANGPTL3 gene expression. The nucleic acid molecule contains or consists of substantially complementary sense and antisense sequences, wherein the sense sequence and / or antisense sequence has a nucleotide length of 14-30 nt. The nucleic acid molecule can better specifically silence an ANGPTL3 gene.

This invention belongs to the field of biomedicine, specifically relating to siRNA targeting the angiopoietin-like protein 3 gene and its applications. The siRNA comprises a sense strand and an antisense strand, wherein the sense strand and the antisense strand are at least partially anticomplementary to form a double-stranded region. The sense strand or antisense strand consists of a 19-nucleotide blunt-ended complementary nucleotide sequence; or a sense strand of 19 nucleotides and an antisense strand of 21 nucleotides with overhanging ends. The siRNA of this invention can comprehensively lower blood lipids, and has good lipid-lowering effects on triglycerides and LDL-C, helping to significantly reduce the risk of atherosclerosis and cardiovascular disease.

The invention generally relates to capturing, amplifying, and sequencing nucleic acids. In certain embodiments, copies of the sense and antisense strands of a duplex template nucleic acid are captured using linked capture probes and multiple binding and extension steps to improve specificity over traditional single binding target capture techniques. Methods of seeding sequencing clusters with sense and antisense strands of a target nucleic acid are also disclosed including identifying the strands using sense-specific barcodes and confirming base calls using two sense-specific sequencing reads. Linked adapters may be used to increase adapter ligation selectively or efficiency and yield.

Provided herein are double-stranded nucleic acid inhibitor molecules having a shortened sense strand with a stem loop structure and an antisense strand. Also provided are methods and compositions for reducing target gene expression and methods and compositions for treating a disease of interest.

The present invention relates to a nucleic acid molecule that inhibits intracellular factor 11 (FXI) gene expression via RNAi, comprising mutually complementary sense sequences and antisense sequences or composed of mutually complementary sense sequences and antisense sequences, and the inhibition rate of said nucleic acid molecule against FXI is significantly superior to that of other small nucleic acid molecules that inhibit FXI expression via RNAi.

This application relates to the field of biotechnology, and particularly to Arg1-targeting double-stranded oligonucleotides and their conjugates, pharmaceutical compositions, and their application in pulmonary fibrosis. The Arg1-targeting double-stranded oligonucleotide comprises a sense strand and an antisense strand, wherein the sense strand and antisense strand are at least partially anticomplementary to form a double-stranded region; the nucleotide sequence of the sense strand comprises a sequence differing from the sequence shown in SEQ ID NO.1 by no more than 3 nucleotides, and the nucleotide sequence of the antisense strand comprises a sequence differing from the sequence shown in SEQ ID NO.2 by no more than 3 nucleotides. Using this Arg1-targeting double-stranded oligonucleotide and its conjugates, or pharmaceutical compositions containing it, to reprogram the nucleic acid of M2 macrophages in pulmonary fibrosis can effectively alter their pro-fibrotic functional state.

Provided is an siRNA that inhibits the expression of an RAGE gene, which siRNA comprises a sense strand and an antisense strand. The provided siRNA has good stability and can be used for efficiently and specifically inhibiting the expression of the RAGE gene, thereby providing important clinical value in the treatment of RAGE-related diseases.

This invention belongs to the field of biomedicine, specifically relating to siRNA that inhibits AR gene expression, comprising a sense strand and an antisense strand, wherein the sense strand and the antisense strand are at least partially anticomplementary to form a double-stranded region, and the sense strand or antisense strand consists of 19-25 nucleotides with blunt ends of complementary nucleotide sequences; or the antisense strand consists of 27 nucleotide sequences with overhangs. The siRNA of this invention can maintain long-term efficacy with a single dose, exhibiting good compliance in patients with chronic diseases such as androgenetic alopecia. Furthermore, it has lower off-target toxicity and fewer side effects compared to small molecule chemical drugs and hormone drugs.

Alternative splicing events in genes can lead to non-productive mRNA transcripts which in turn can lead to aberrant or reduced protein expression, and therapeutic agents which can target the alternative splicing events in the genes can modulate the expression level of functional proteins in patients and / or inhibit aberrant protein expression. Such therapeutic agents can be used to treat a condition or disease caused by protein deficiency.

This invention relates to the field of biomedical technology, and discloses a siRNA that specifically inhibits LILRB4 gene expression and its applications. The siRNA contains a completely inversely complementary sense strand and an antisense strand, the nucleotide sequences of which are any pair as shown in SEQ ID NO. 1 and 2, SEQ ID NO. 3 and 4, SEQ ID NO. 5 and 6, SEQ ID NO. 7 and 8, SEQ ID NO. 9 and 10, SEQ ID NO. 11 and 12, SEQ ID NO. 13 and 14, SEQ ID NO. 15 and 16, SEQ ID NO. 17 and 18, or SEQ ID NO. 19 and 20. This invention also provides the application of this siRNA in the preparation of pharmaceuticals. The siRNA pharmaceutical composition provided by this invention can effectively silence LILRB4 gene expression, inhibit the infiltration of tumor cells into normal tissues and organs, and enhance T cell activity.

This invention provides an siRNA that inhibits the expression of the MMP7 gene, comprising a sense strand and an antisense strand. The siRNA according to this invention has good stability, excellent MMP7 gene inhibitory activity, negligible cytotoxicity and immunostimulant activity, and can significantly reduce MMP7 protein levels at the animal level. It has significant clinical value in the treatment of diseases or conditions that benefit from the reduction of MMP7 levels or inhibition of its expression.

Provided are a double-stranded oligonucleotide, a conjugate and a composition, as well as a use therefor, relating to the technical field of nucleic acid drugs. The double-stranded oligonucleotide comprises a sense strand and an antisense strand, 17-23 nucleotides of the sense strand and the antisense strand being at least partially reverse complementary, to form a duplex region; the duplex region contains at least five phosphorothioate nucleotide linkages. The double-stranded oligonucleotide has at least one overhang, and the overhang is not located at the 5' end of the antisense strand; the overhang comprises at least one nucleotide modified with [2'-R1-2'-R2].

Provided herein are, inter alia, agents (e.g., RNAi agents, dsRNA agents) comprising a sense strand and an antisense strand targeting TNFAIP3 (e.g., hTNFAIP3); and methods of manufacturing and pharmaceutical compositions comprising the same. Further provided herein are methods of utilizing the RNA agents (e.g., RNAi agents, dsRNA agents) including, e.g., methods of inhibiting or decreasing TNFAIP3 expression (e.g., mRNA expression), methods of treating TNFAIP3 associated diseases, and methods of treating proinflammatory (e.g., autoimmune) diseases (e.g., inflammatory bowel disease); and cancer.

The invention provides double-stranded oligonucleotide targeting INHBE gene, a conjugate and a composition, and relates to the technical field of nucleic acid drugs. The double-stranded oligonucleotide comprises a positive-sense strand and an antisense strand, and the antisense strand and the positive-sense strand are complementary or basically complementary; the positive-sense strand comprises a nucleotide sequence identical or substantially identical to at least 15 contiguous nucleotides in the SEQ ID NO: 309 sequence, the substantially identical means that the positive-sense strand has no more than 3 nucleotide differences from the at least 15 contiguous nucleotides in the SEQ ID NO: 309 sequence. The double-stranded oligonucleotide can effectively inhibit the INHBE gene and treat patients suffering from metabolic disorders or metabolic syndromes and related diseases such as diabetes, hypertension and cardiovascular diseases.

The present invention provides a method for preparing an siRNA for treating α1-antitrypsin deficiency. The siRNA is Fazirsiran. Fazirsiran is a double-stranded RNA composed of a complementarily paired sense strand and antisense strand. The preparation method comprises: mixing sense strand substrates, antisense strand substrates, and an RNA ligase, and using the RNA ligase to catalyze the linkage between the sense strand substrates and between the antisense strand substrates by means of phosphodiester bonds, to obtain a sense strand and an antisense strand, thereby obtaining Fazirsiran, wherein the sense strand substrates can form the sense strand, and the antisense strand substrates can form the antisense strand. Compared with the preparation of Fazirsiran by means of chemical synthesis, the product obtained by the preparation method of the present application has higher purity and fewer impurities, and the reaction conditions are mild, facilitating industrial large-scale production.

Provided are an INHBE gene-targeted double-stranded oligonucleotide, a conjugate, and a composition, which relate to the technical field of nucleic acid drugs. The double-stranded oligonucleotide comprises a sense strand and an antisense strand. The antisense strand is complementary or substantially complementary to the sense strand; the sense strand comprises a nucleotide sequence identical or substantially identical to at least 15 contiguous nucleotides in a sequence of SEQ ID NO: 309, and said substantially identical means that there is no more than three nucleotide differences between the sense strand and the at least 15 contiguous nucleotides in the sequence of SEQ ID NO: 309. The double-stranded oligonucleotide can effectively inhibit the INHBE gene and treat patients suffering from metabolic diseases or metabolic syndrome and related diseases such as diabetes, hypertension and cardiovascular diseases.

The present invention addresses the problem of providing siRNA that targets a WRN helicase gene, is based on a novel target sequence, and brings about better effects than conventional types of siRNA.　Provided is siRNA which targets a WRN helicase gene and comprises: (a) a sense strand comprising the nucleotide sequence represented by SEQ ID NO: 1 and an antisense strand comprising the nucleotide sequence represented by SEQ ID NO: 2; (b) a sense strand comprising the nucleotide sequence represented by SEQ ID NO: 3 and an antisense strand comprising the nucleotide sequence represented by SEQ ID NO: 4; (c) a sense strand comprising the nucleotide sequence represented by SEQ ID NO: 5 and an antisense strand comprising the nucleotide sequence represented by SEQ ID NO: 6; (d) a sense strand comprising the nucleotide sequence represented by SEQ ID NO: 7 and an antisense strand comprising the nucleotide sequence represented by SEQ ID NO: 8; (e) a sense strand comprising the nucleotide sequence represented by SEQ ID NO: 9 and an antisense strand comprising the nucleotide sequence represented by SEQ ID NO: 10; (f) a sense strand comprising the nucleotide sequence represented by SEQ ID NO: 11 and an antisense strand comprising the nucleotide sequence represented by SEQ ID NO: 12; or (g) a sense strand comprising the nucleotide sequence represented by SEQ ID NO: 13 and an antisense strand comprising the nucleotide sequence represented by SEQ ID NO: 14.

The invention discloses a siRNA molecule targeting a human SLC25A17 gene, the siRNA molecule comprises a positive-sense strand and an antisense strand, the specific sequence is as follows: the positive-sense strand: 5 '-CCUUGGAUGUGUUCAUCAUNn-3', the antisense strand: 5 '-AUGAUGAACACAUCAAGGNn-3', N in the positive-sense strand and N in the antisense strand are the same or different, and are respectively and independently cytosine C, uracil U, guanine G, adenine A, deoxycytosine dC, deoxyguanine dG, deoxyadenine dA or deoxythymine dT; n represents the number of N, and n = 0, 1 or 2. The invention further discloses application of the siRNA molecule of the targeted human SLC25A17 gene, and the siRNA molecule is applied to liver cancer treatment by efficiently inhibiting the expression level of SLC25A17.

Provided herein is a lipid nanoparticle comprising an encapsulated oligonucleotide molecule, wherein the oligonucleotide molecule is single-stranded or double-stranded and has a length of between 5 and 500 nucleotides; and 20 to 70 mol % of a neutral lipid content relative to total lipid present in the lipid nanoparticle, an ionizable lipid; a sterol; and optionally a hydrophilic polymer-lipid conjugate.

Provided are an siRNA for inhibiting the expression of the apolipoprotein C3 gene, and a pharmaceutical composition and a conjugate containing the siRNA. Each nucleotide in the siRNA is, respectively and independently, a modified or unmodified nucleotide; the siRNA contains a sense strand and an anti-sense strand; the sense strand includes nucleotide sequence I; nucleotide sequence I has the same length as the nucleotide sequence as shown in SEQ ID NO: 1, and not more than three nucleotides are different; the anti-sense strand contains nucleotide sequence II; and nucleotide sequence II has the same length as the nucleotide sequence as shown in SEQ ID NO: 2, and not more than three nucleotides are different. The siRNA provided by the present disclosure and the pharmaceutical composition and the conjugate thereof can effectively treat and / or prevent dyslipidemia.

Provided is a method for preparing siRNA for inhibiting FXI gene expression. The siRNA is Fitusiran, and the Fitusiran is a double-stranded RNA composed of a sense strand and an antisense strand that complement and are paired with each other. The preparation method comprises: mixing sense strand substrates, antisense strand substrates and an RNA ligase, wherein the sense strand substrates can constitute the sense strand, the antisense strand substrates can constitute the antisense strand, the sense strand substrates and the antisense strand substrates are connected via hydrogen bonds formed by means of complementary base pairing, and no linkage is formed between head and tail bases of the sense strand substrates and between head and tail bases of the antisense strand substrates, thereby forming a nicked double-stranded nucleotide structure; and ligating the bases at both ends of the nick via a phosphodiester bond using the RNA ligase to form the Fitusiran. The preparation method can solve the problem of Fitusiran prepared by means of the prior art having low purity.

The present application provides an RNA inhibitor or a pharmaceutically acceptable salt thereof that inhibits the expression of the LPA gene. The RNA inhibitor is formed by base pairing between a sense strand and an antisense strand having a chain length of 15-30, preferably 19-23, and at least 85% of the bases of the sense strand and the antisense strand are complementary. The -OH at the 2'-position of the glycosyl nucleotides of some or all of the sense strand and / or the antisense strand may be substituted with a fluorine or methoxy group, and the phosphate ester bond between three adjacent nucleotides at at least one end of the sense strand and / or the antisense strand may be thiolated. The structure of the RNA inhibitor may further include carrier structures 5'MVIP and 3'MVIP. The RNA inhibitor provided herein interferes with the translation template function of LPA mRNA, efficiently and continuously inhibits the expression of the LPA gene, and can be used to treat and / or prevent diseases associated with elevated levels of LPA(a).