301 results about "Sense strand" patented technology

This disclosure relates to an siRNA-lipid conjugate of formula Y-L-(H)n. Y is an siRNA molecule. L is a linker covalently bonded to Y and H, each H is independently a hydrophobic chain comprising 5 to 50 carbon atoms, n is 1, 2, or 3, and linker L is bonded to the 3′ end of the sense strand of the siRNA.

The invention discloses a verticillium dahliae virulence gene, a verticillium dahliae virulence protein and application. The invention relates to the technical field of biology, and provides a method for preventing and treating cotton verticillium wilt based on RNAi (RNA interference) as well as related components and application thereof. Specifically, the invention discloses application of the verticillium wilt prevention and treatment by a method for inhibiting or silencing the expression of verticillium dahliae pathogenic gene VdHDAC (coding protein of the verticillium dahliae pathogenic gene VdHDAC is shown as SEQ ID NO: 3), the core of the verticillium wihliae pathogenic gene VdHDAC is to provide dsRNA molecules capable of targeting the gene, and the positive-sense strand of the dsRNA molecules is preferably selected from SEQ ID NO: 5, SEQ ID NO: 8, SEQ ID NO: 9 or SEQ ID NO: 11. Based on the molecule, the invention further provides a recombinant vector containing the coding sequence, a recombinant microorganism, a transgenic disease-resistant plant and an RNAi pesticide preparation. The scheme can be realized through host-induced gene silencing, microorganism-mediated gene silencing or preparation treatment and the like, the virulence of pathogenic bacteria can be effectively reduced, and a new technical approach is provided for green prevention and control of verticillium wilt.

The present invention relates to an siRNA for inhibiting FXI gene expression, an siRNA conjugate, a pharmaceutical composition containing same, and the use thereof. Each nucleotide in the siRNA is independently a modified or unmodified nucleotide, and the siRNA contains a sense strand and an antisense strand. The siRNA and the conjugate and pharmaceutical composition thereof can effectively treat and / or prevent diseases associated with FXI gene overexpression.

This vector for nucleic acid introduction contains a nucleotide sequence that encodes a Cas protein, a nucleotide sequence that encodes a guide RNA, and a nucleotide sequence of a nucleic acid to be introduced. The guide RNA targets an intron adjacent to the 5' side, with reference to a sense strand, of an exon that includes a stop codon. Also provided is a nucleic acid introduction method comprising a step for introducing a nucleic acid to be introduced through non-homologous end joining by targeting an intron that is adjacent to the 5' side, with reference to a sense strand, of an exon that includes a stop codon.

The present disclosure provides double stranded ribonucleic acid (dsRNA) agents for inhibiting expression of a target gene, comprising an antisense strand which is complementary to the target gene; a sense strand which is complementary to the antisense strand and forms a double stranded region with the antisense strand; at least one alpha-v-beta-6 (αvβ6) integrin targeting ligand that mediates delivery to muscle tissue conjugated to at least one strand; and at least one in vivo delivery enhancing moiety conjugated to one or more internal positions on at least one strand. The present disclosure also provides compositions comprising such dsRNA agents, and methods of use thereof for treating a subject having a disorder that would benefit from reduction in expression of the target gene.

The present invention belongs to the technical field of medicine and provides a carbocyclic nucleoside-containing siRNA conjugate, and a pharmaceutical composition and a use thereof. The sense strand and / or antisense strand of the siRNA conjugate comprises at least one carbocyclic nucleoside represented by structural formula (I) below. The sense strand comprises at least 16 consecutive nucleotides of the nucleotide sequence 5'-GUCAUCCACAAUGAGAGUACA-3', and the antisense strand comprises at least 18 consecutive nucleotides of the nucleotide sequence 5'-UGUACUCUCAUUGUGGAUGACGA-3'. The carbocyclic nucleoside-containing siRNA conjugate provided by the present invention can be used for treating, preventing, and / or alleviating AGT-related diseases, such as hypertension.

To provide dsRNA molecules which are advantageous for inhibition of target gene expression while having reduced off-target gene silencing effects.SOLUTION: The present invention relates to double-stranded RNA (dsRNA) agent capable of inhibiting the expression of a target gene. The antisense strand of the dsRNA molecule comprises at least one thermally destabilizing nucleotide occurring at a seed region; the dsRNA comprises at least four 2'-fluoro modifications; and the sense strand of the dsRNA molecule comprises a ligand, where the ligand is an ASGPR ligand.SELECTED DRAWING: None

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 disclosure relates to a nucleoside analogue and a use thereof. The nucleoside analogue is a compound shown in formula (Ia) or a prodrug thereof. The nucleoside analogue can enhance targeted delivery of oligonucleotide drugs to nervous system cells, thereby increasing the inhibition rate of the oligonucleotide drugs delivered in a targeted manner on expression of specific genes in the nervous system cells, or enabling the oligonucleotide drugs delivered in a targeted manner to achieve the purpose of preventing and / or treating pathological conditions or diseases caused by abnormal expression of the specific genes in the nervous system cells. The present disclosure also relates to a nucleotide analogue-containing double-stranded oligonucleotide and a use thereof. The double-stranded oligonucleotide comprises a sense strand and an antisense strand, each strand has 17-25 modified and / or unmodified nucleotides, and the antisense strand and the sense strand are complementary to form a duplex region; the sense strand and / or the antisense strand contains at least one nucleotide analogue represented by the structure of formula (100), or a tautomer, or stereoisomer, or pharmaceutically acceptable salt thereof; the double-stranded oligonucleotide can effectively treat and / or prevent pathological conditions or diseases caused by abnormal expression of specific genes in nervous system cells.

Provided are an siRNA targeting AZGP1 and the use thereof in the preparation of a drug for tumor treatment. An siRNA molecule for inhibiting the expression of an AZGP1 gene may be AZGP1-1, AZGP1-2, AZGP1-3, AZGP1-4, AZGP1-5, AZGP1-6 or AZGP1-7. The siRNA molecule comprises a sense strand and an antisense strand. The sense strand can be at least partially reverse complementary to the antisense strand to form a double-stranded region. The provided siRNA molecule targeting the AZGP1 gene can inhibit the invasion, proliferation and epithelial-mesenchymal transition of breast cancer cells, and is of great significance for treating cancer, especially breast cancer, by inhibiting the expression of the AZGP1 gene.

The invention discloses siRNA capable of knocking down Pr18a9 gene expression and application of the siRNA, and relates to the technical field of biological medicine. The invention provides a positive-sense strand sequence and an antisense strand sequence of the siRNA, and the siRNA is used for preparing a preparation for promoting Schwann cell survival. According to the invention, the Prl8a9 gene of SCs is knocked down by virtue of a small interfering RNA technology; by improving the proliferation and migration capabilities of the Schwann cells, the apoptosis rate of the Schwann cells is reduced, and the survival rate of the Schwann cells is further improved. Meanwhile, a transcriptome sequencing technology is applied, key genes and pathways of Schwann cells treated by siPr18a9 are deeply excavated, and a theoretical support is provided for research on a repair mechanism after peripheral nerve injury.

The present invention provides an siRNA that inhibits angiopoietin-like 4 (ANGPTL4) gene expression, wherein the siRNA comprises a sense strand and an antisense strand, wherein the antisense strand comprises at least 17 continuous nucleotides that differ by no more than 4 nucleotides from the nucleotide sequences as shown in SEQ ID NO: 143, and the antisense strand is 17 to 30 nucleotides in length; the sense strand is 17 to 30 nucleotides in length and is at least partially complementary to the antisense strand. The siRNA, siRNA conjugate, and pharmaceutical composition provided in the present invention exhibit good stability, ANGPLT4 gene inhibitory activity, and immunostimulation, and can significantly reduce ANGPTL4 protein concentrations at the animal level.

Provided in the present invention are a siRNA for inhibiting the expression of complement component C5, the use thereof, and a product thereof, belonging to the technical field of small-molecule drugs and relating to the design and use of siRNA for C5 genes. The siRNA of the present invention comprises a sense strand and an antisense strand, wherein the sense strand comprises a nucleotide sequence as shown in SEQ ID NO. 1-SEQ ID NO. 546, and the antisense strand comprises a nucleotide sequence as shown in SEQ ID NO. 547-SEQ ID NO. 1092. Provided in the present invention is a brand new siRNA which can effectively inhibit the expression of complement component C5.

The present application relates to siRNA for inhibiting NR1H3 gene expression and its modification and conjugate and application, belong to the field of biotechnology. The present application provides a kind of siRNA for inhibiting NR1H3 gene expression, its sense strand includes the first nucleotide sequence as shown in any one of SEQ ID NO.4, SEQ ID NO.15, SEQ ID NO.33 or SEQ ID NO.74-SEQ ID NO.80, its antisense strand includes the second nucleotide sequence as shown in any one of SEQ ID NO.40, SEQ ID NO.51, SEQ ID NO.70 or SEQ ID NO.81-87. Experiments have confirmed that the siRNA of the present application and its modification and conjugate are all higher inhibitory activity to NR1H3, therefore, in the preparation of drug for treating disease related to lipid metabolism has very application prospect.

The application discloses a kind of preparation and application of multi-target small nucleic acid drug based on small activation RNA technology, and is related to the field of biotechnology.The preparation method of the multi-target small nucleic acid drug includes the following steps: (1) selecting at least two anti-disease genes according to target disease;(2) intercepting the sequence of 1000 base pairs of the promoter region upstream of the coding region of the anti-disease gene;(3) according to the promoter sequence, avoid CpG island and locate the segment of species conservation, and cut a sequence containing 19 base length as a sense strand;(4) design an antisense strand according to the sense strand, and the 19 base of the antisense strand and the sense strand are completely complementary;(5) add two deoxythymine or uracil to the 3' end of each chain.The multi-target small nucleic acid drug has good therapeutic effect on heart failure, and has strong cancer cell killing ability and inhibition ability of cancer cell migration, and has wide application prospect.

This invention discloses a trimethyl chitosan-hyaluronic acid-FMNL2 siRNA nanomedicine and its applications. The siRNA molecule consists of a sense strand and an antisense strand, which are anti-complementary to form a double-stranded RNA structure. Each of the sense and antisense strands independently contains two pendant deoxythymidines at its 3' end. The nanomedicine uses trimethyl chitosan as its core framework, efficiently encapsulating the siRNA molecule through electrostatic interactions, and then modifying hyaluronic acid through electrostatic interactions to form core-shell structured nanoparticles. This invention forms a complete technology chain from target validation, siRNA sequence design, nanodelivery system construction, in vivo and in vitro efficacy verification to the development of combination drug strategies. It also provides quantifiable efficacy evaluation biomarkers, offering a clear basis for clinical patient screening and efficacy monitoring.

The invention provides a C4B gene inhibitor composition and application thereof, and belongs to the technical field of nucleic acid drugs. The double-stranded oligonucleotide comprises a positive-sense strand and an antisense strand, the positive-sense strand comprises at least 15 continuous nucleotides in any sequence as shown in SEQ ID NO: 1-SEQ ID NO: 180 or a nucleotide sequence, and the difference between the at least 15 continuous nucleotides and the nucleotide sequence is not more than 3 nucleotides; and / or the antisense strand comprises at least 15 consecutive nucleotides in any sequence as shown in SEQ ID NO: 181-SEQ ID NO: 360 or a nucleotide sequence which is different from the at least 15 consecutive nucleotides by not more than 3 nucleotides. The double-stranded oligonucleotide can inhibit the expression of the complement C4B gene of mammals, and achieves the effects of relieving, treating and / or preventing complement C4B-mediated diseases or symptoms.

The present invention relates to siRNA and siRNA conjugates for inhibiting blood coagulation factor XII (FXII) gene expression, a pharmaceutical composition comprising the same, and uses thereof. Each nucleotide in the siRNA is independently modified or unmodified nucleotide, and the siRNA contains a positive-sense strand and an antisense strand. The siRNA as well as the conjugate and the pharmaceutical composition thereof can be used for effectively treating and / or preventing diseases related to FXII gene overexpression.

Relates to the technical field of nucleic acid drugs, and particularly provides a double-stranded oligonucleotide for inhibiting complement factor B (CFB) gene expression, the double-stranded oligonucleotide comprises a sense strand and an antisense strand, the positive-sense strand comprises at least 15 continuous nucleotides in any sequence as shown in SEQ ID NO: 1-SEQ ID NO: 255 in a table 1 or a nucleotide sequence which is different from the at least 15 continuous nucleotides by not more than 3 nucleotides; and / or the antisense strand comprises at least 15 contiguous nucleotides in any sequence as shown in SEQ ID NO: 256-SEQ ID NO: 510 in the table 1 or a nucleotide sequence which is different from the at least 15 contiguous nucleotides by not more than 3 nucleotides. The double-stranded oligonucleotide can inhibit CFB gene expression in cells and achieve the effects of relieving, treating and / or preventing diseases or symptoms mediated by CFB gene expression abnormity.

This disclosure provides siRNAs that target and regulate HBV gene expression and their applications. The double-stranded RNAi agent comprises an antisense strand and a sense strand complementary to the antisense strand forming the double-stranded region. The nucleotide sequence of the antisense strand is shown in SEQ ID NO:13, or the nucleotide sequence of the antisense strand is a modified sequence of the sequence shown in SEQ ID NO:13. Cellular and animal experimental results show that the double-stranded RNAi agent provided in this disclosure can significantly reduce the expression of one or more HBV genes, block the viral life cycle, and can be used to develop drugs for treating HBV gene expression-related diseases.

This invention provides a double-stranded ribonucleic acid interference (dsRNAi) agent that targets the microtubule-associated protein tau (MAPT) gene. [Solution] A double-stranded ribonucleic acid (dsRNA) agent for inhibiting MAPT expression is provided, wherein the dsRNA agent comprises a sense strand and an antisense strand that form a double-stranded region, and the sense strand and antisense strand each contain a nucleotide sequence having a specific sequence and at least 15 consecutive nucleotides that differ by 3 or fewer nucleotides.

The application relates to the technical field of biological medicine, in particular to a preparation method of anti-aspergillus niger siRNA and a complex preparation thereof, wherein the anti-aspergillus niger siRNA comprises siR266 for a PmrA gene and / or siR505 for a SarA gene, the sequence of a sense strand and an antisense strand of the siR266 is shown in SEQ ID NO: 3-4 respectively, and the sequence of a sense strand and an antisense strand of the siR505 is shown in SEQ ID NO: 7-8 respectively. Wherein, the complex preparation adopts protamine sulfate as a carrier, and forms a complex with the anti-aspergillus niger siRNA. The complex preparation prepared by the application can effectively inhibit aspergillus niger, and can be applied to food preservation, postharvest protection of fruits and vegetables, and mildew prevention of daily necessities and the like, and is suitable for developing corresponding anti-fungal products.

To provide an iRNA composition that affects RNA-induced silencing complex-mediated cleavage of an RNA transcript of a gene encoding angiotensinogen (AGT).SOLUTION: Provided is a double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of AGT, the dsRNA agent comprising a sense strand and an antisense strand that form a double stranded region. The present invention also provides methods of using such RNAi agents to inhibit expression of an AGT gene and methods of preventing and treating an AGT-associated disorder, e.g., high blood pressure.SELECTED DRAWING: None

The invention relates to a preparation method of a small nucleic acid combined microneedle and application of the small nucleic acid combined microneedle to skin light injury repair, and particularly discloses a microneedle composition which comprises a compound of SNAP25 specific siRNA and nano-selenium and hyaluronic acid, the nucleotide sequence of a positive-sense strand of the siRNA is shown as SEQ ID NO.1, and the nucleotide sequence of an antisense strand of the siRNA is shown as SEQ ID NO.2. The invention further discloses a preparation method of the microneedle composition. The microneedle composition provided by the invention can realize stable delivery of siRNA, inhibit UV-induced skin photoaging related gene expression, increase repair of skin extracellular matrix and significantly improve skin light damage, and is suitable for clinical transformation application.

One aspect of the present invention relates to a double-stranded RNA (dsRNA) agent for modulating the expression of a target gene in the central nervous system (CNS), comprising: an antisense strand complementary to the target gene in the CNS; a sense strand complementary to the antisense strand; and one or more saturated or unsaturated C RNAs conjugated onto at least one strand via a linker or carrier as appropriate. 22 The present invention relates to a dsRNA agent comprising one or more lipophilic moieties containing a hydrocarbon chain. Another aspect of the present invention relates to a pharmaceutical composition comprising a dsRNA agent. Another aspect of the present invention relates to a method for modulating the expression of a target gene in CNS cell genes and a method for treating or preventing CNS damage in a subject, comprising administering a therapeutically effective amount of a dsRNA agent to cells or a subject.

Provided are a double‑stranded RNA composition for modulating DGAT2 expression, a conjugate thereof, a pharmaceutical composition comprising same, and a use thereof. The double-stranded RNA comprises a sense strand and an antisense strand, and each nucleotide in the double-stranded RNA is independently a modified or unmodified nucleotide; the sense strand comprises one nucleotide sequence selected from the nucleotide sequences shown in SEQ ID NOs: 1-86 or a nucleotide sequence having no more than 3 nucleotide differences from the above sequences, and the antisense strand comprises one nucleotide sequence selected from the nucleotide sequences shown in SEQ ID NOs: 87-172 or a nucleotide sequence having no more than 5 nucleotide differences from the above sequences. The double-stranded RNA, the conjugate thereof and the pharmaceutical composition comprising same can be delivered to the liver by means of small nucleic acid delivery technology, and are expected to provide a safer and more effective therapeutic plan for patients with MASH-associated metabolic diseases.

An siRNA inhibiting xanthine oxidase (XO) gene expression, a pharmaceutical composition containing the siRNA, a siRNA conjugate, and an application of the siRNA in the preparation of drugs for treating and / or preventing uric acid metabolism disorder or diseases or physical conditions caused by uric acid metabolism disorder. Each nucleotide in the siRNA is an independent modified or unmodified nucleotide, and the siRNA contains a sense strand and an antisense strand.

Provided herein are, inter alia, agents (e.g., dsRNA agents comprising a sense strand and an antisense strand; RNAi agents, ssRNAs, ASOs) comprising a sense strand and an antisense strand targeting BCL11A (e.g., hBCL11A); and methods of manufacturing and pharmaceutical compositions comprising the same. Further provided herein are methods of utilizing the agents (e.g., dsRNA agents comprising a sense strand and an antisense strand; RNAi agents, ssRNAs, ASOs) including, e.g., methods of inhibiting or decreasing BCL11A expression (e.g., mRNA expression), methods of treating BCL11A associated diseases.

This invention provides RNAi agents, such as dsRNA agents, that target the G protein-coupled receptor 75 (GPR75) gene. It also provides methods for using such RNAi agents to inhibit the expression of the GPR75 gene in a subject, and methods for treating or preventing GPR75-related diseases such as weight disorders, e.g., obesity. [Solution] A double-stranded ribonucleic acid (dsRNA) agent for inhibiting the expression of the GPR75 gene in cells is provided, comprising a sense strand and an antisense strand that form a double-stranded region, wherein the antisense strand comprises a region complementary to a portion of the mRNA encoding the GPR75 gene, each strand is independently 14 to 30 nucleotides long, and the sense strand or antisense strand is conjugated to one or more lipophilic portions.