33 results about "Antisense nucleic acid" patented technology

The present invention relates to agents, compositions, and methods for treating or ameliorating symptoms of cancer. Exemplary synergistic therapies include the use of antisense oligonucleotide agents to suppress expression of TGF-β2, alone and in combination with interferon-gamma. One or more biomarkers can be used to select subjects for treatment.

This invention provides a drug that efficiently skips the 50th exon of the human dystrophin gene. [Solution] An antisense oligomer or a pharmaceutically acceptable salt thereof or a hydrate thereof that induces skipping of the 50th exon of the human dystrophin gene is provided.

The present invention provides a single-stranded antisense oligonucleotide or pharmaceutically acceptable salt thereof for regulating the expression and / or function of the ATXN7 gene. In the single-stranded antisense oligonucleotide, each nucleotide is bonded by a phosphate group and / or modified phosphate group. The single-stranded antisense oligonucleotide includes a gap region, a 3' wing region bonded to the 3' terminal of the gap region, and a 5' wing region bonded to the 5' terminal of the gap region. The gap region is a deoxyribose-constituted nucleic acid in which a nucleic acid modified by a sugar moiety may be included. The 3' wing region and the 5' wing region are modified nucleic acids. The sugar modification constituting the single-stranded antisense oligonucleotide is a modified nucleic acid represented by formula (A1). The single-stranded antisense oligonucleotide has a base length of 12-30 mer. The base sequence of the antisense oligonucleotide is: a base sequence having a sequence identity of 90-100% with a base sequence that is complementary to at least one target region constituted at the same base length as the antisense oligonucleotide in the base sequence shown in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, or SEQ ID NO: 5; a base sequence that is complementary to the base sequence obtained by deleting, substituting, inserting, or adding one or more bases in the target region; or a base sequence that, under stringent conditions, hybridizes with an oligonucleotide having the target region.

This application provides antisense nucleic acid compounds that reduce the levels of certain nutrients in neurons of the central nervous system. UBE3A This application also provides compositions comprising antisense nucleic acid compounds and their application in the prevention or treatment of overdose in subjects. UBE3A Use in methods related to mRNA and / or UBE3A peptide levels.

In the present description, provided are an antisense oligomer that enables simultaneous skipping of a plurality of exons in a target pre-mRNA and a medicinal composition comprising the oligomer. In the present description, also provided is an antisense oligomer enabling simultaneous skipping of two or more exons, said exons being consecutive in numerical order, from a target pre-mRNA, a pharmaceutically acceptable salt thereof or a hydrate of the same, wherein the antisense oligomer contains a base sequence that is complementary to the base sequence of a region containing the vicinity of a donor of any intron in the target pre-mRNA or a region containing the vicinity of an acceptor of any intron in the target pre-mRNA or a partial base sequence thereof.

Described herein, inter alia, are compounds for treating cancer and methods of use. This disclosure features chemical entities (e.g., small hairpin RNAs (shRNAs), micro RNA (miRNAs), small interfering RNA (siRNAs), small molecule inhibitors, antisense nucleic acids, peptides, viruses, CRISPR-sgRNAs, or combinations thereof) that inhibit one or more of m6A writers (e.g., methyltransferase like 3 (Mettl3 or MT-A70) or methyltransferase like-14 (Mettl14)), m6Am writers (e.g., phosphorylated CTD interacting factor I (PCIF 1), or Mettl3 / 14), m6A erasers (e.g., fat-mass and obesity-associated protein (FTO) or ALKB homolog 5 (ALKBH5)), m6Am erasers (e.g., FTO), m6A readers (e.g., YTH domain-containing family proteins (YTHs)), YTF domain family member 1 (YTHDF 1), YTF domain family member 2 (YTHDF 2), YTF domain family member 3 (YTHDF 3), or tyrosine-protein phosphatase non-receptor type 2 (PTPN2).

The present invention provides a novel linkage-type antisense oligomer that induces exon skipping by targeting base sequences at two different sites in the same exon of the dystrophin gene, and a therapeutic agent for muscular dystrophy comprising the oligomer.SOLUTION: It has been found that an antisense oligomer obtained by linking oligomers targeting two different sites of exon 45 of the human dystrophin gene can induce skipping of the exon.SELECTED DRAWING: None

To provide an agent for highly efficiently skipping an exon.SOLUTION: The present invention provides an antisense oligomer in which two or more unit oligomers targeting sequences that are not contiguous or overlapping with each other in the same exon are linked.SELECTED DRAWING: None

The application provides an antisense nucleic acid targeting a KRAS gene, a pharmaceutical preparation thereof and an application thereof, and belongs to the technical field of biological medicines.The nucleotide sequence of the antisense nucleic acid comprises at least one of SEQ ID NO:1 to SEQ ID NO:7; the nucleotide sequence of the antisense nucleic acid further comprises a modified nucleotide sequence of SEQ ID NO:1 and a modified nucleotide sequence of SEQ ID NO:8.The antisense nucleic acid can target the 3'-UTR region of mRNA of KRAS, down-regulate the corresponding mRNA and various mutants thereof, inhibit tumor cell growth, the pharmaceutical preparation thereof can deliver the target antisense nucleic acid to a tumor site and exert a significant inhibitory effect, and has great application potential in the field of tumor gene therapy of KRAS mutation.

Provided are antisense nucleic acids, a splicing promotor, and a pharmaceutical composition that, by inhibiting binding of a RNA-binding protein HNRNPA1 to an exitron more effectively than with conventional methods, can improve splicing abnormalities in an exitron of TDP-43, that can effectively suppress functional deterioration of intranuclear TDP-43 associated with abnormal accumulation of TDP-43, and that can be applied for treating neurodegenerative disorders. The present invention pertains to: antisense nucleic acids which promote splicing of TDP-43, which target a target sequence from position 136 to position 170 or from position 291 to position 339 in the base sequence represented by SEQ ID NO. 1, and which each have a base sequence complementary to a sequence formed of consecutive 10-30 bases in the target sequence; and a splicing promotor and a pharmaceutical composition containing the antisense nucleic acids.

Disclosed herein are systems for modifying nucleic acid splicing of a target RNA, e.g. SCN1A mRNA. The systems can be used in methods, e.g., methods of treating a genetic disorder, e.g., epilepsy. The systems can include an expression system or a modified small nuclear RNA (snRNA) that includes an exon splicing silencer (ESS) sequence and an antisense nucleic acid sequence that targets a target RNA.

The present invention provides oligonucleotides, referred to as cyclic structure oligonucleotides ("CSO"), comprising the functional domains, cyclization domains, and linker fragments described herein, compositions comprising the same, and methods of use thereof. The design of this cyclic oligonucleotide remains cyclic until it hybridizes with the target RNA in the presence.

This invention belongs to the field of liver disease research and biomedicine, specifically relating to the application of reagents targeting and inhibiting OXCT1 in combination with BHB or pharmaceutically acceptable salts thereof in the preparation of anti-HCC drugs. The reagents inhibiting OXCT1 include: siRNA, shRNA, antisense nucleic acid, and gene editing reagents that reduce OXCT1 expression; and small molecule inhibitors, peptides, antibodies, or fusion proteins that inhibit OXCT1 enzyme activity. This invention proposes a novel therapeutic strategy of targeting and inhibiting OXCT1 in combination with BHB. Studies have shown that targeting and inhibiting OXCT1 can block the pro-cancer metabolic pathway of BHB, reducing the effective concentration of BHB for its anti-cancer effect, enabling it to achieve significant anti-cancer effects at clinically tolerable concentrations and exert a synergistic anti-tumor effect. This invention solves the problem of limited clinical application of high-concentration BHB and provides a new combination therapy regimen with clinical translational potential for hepatocellular carcinoma.

This invention provides a drug that efficiently skips the 53rd exon of the human dystrophin gene. [Solution] The present invention provides an oligomer that enables skipping of the 53rd exon of the human dystrophin gene.

Disclosed is a method of treating a subject who has a neurological disease. In one aspect, the method includes a step of administering an effective dose of a SYF2 antisense or inhibitory nucleic acid to a subject in need thereof, thereby restoring nuclear localization of TDP-43.

The invention relates to isolated antisense molecule capable of inhibiting the expression of the LMNA gene in a mammalian cell, wherein said antisense molecule comprises an anti-sense nucleic acid strand which is substantially complementary to a target region of a transcript encoded by the LMNA gene, wherein said antisense nucleic acid strand is at least complementary to SNP rs538089, rs505058 or rs4641 in said target region.

The present invention provides an antisense oligomer having the base sequence depicted in SEQ ID NO: 26, an antisense oligomer having a base sequence resulting from substitution, deletion, insertion, or addition of 1 to 6 bases in the base sequence depicted in SEQ ID NO: 26, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable hydrate thereof, an oligonucleotide conjugate in which the antisense oligomer is bound with a molecule capable of binding to an asialoglycoprotein receptor, and a pharmaceutical composition containing the same.

Modified antisense mucleic acid molecules ending with or without chain terminating bases targeting the HIV-1 viral genomic RNA 3′ LTR region, and uses thereof for inhibiting HIV-1 replication and infection, are disclosed. The antisense mucleic acid molecules more specifically target a sequence corresponding to about nucleotide 9628 to about nucleotide 9642 of HIV-1 clone pNL4-3.

The present disclosure relates to compositions and methods for treating liver cancers, especially hepatocellular carcinoma, using antisense (AS) nucleic acids directed against Insulin- like Growth Factor 1 Receptor (1GF-1R). The AS may be administered to the patients systemically, or may be used to produce an autologous cancer cell vaccine. In embodiments, the AS are provided in an implantable irradiated biodiffusion chamber comprising tumor cells and an effective amount of the AS. The chambers are irradiated and implanted in the abdomen of subjects and stimulate an immune response that attacks tumors distally. The compositions and methods disclosed herein may be used to treat many different kinds of liver cancer.

Disclosed is a pesticide for spider mites belonging to the family Tetranychidae, the pesticide comprising any of the following (a) to (c): (a) a double-stranded RNA that has an RNAi effect on syntaxin genes and / or the syntaxin12 gene; (b) an antisense nucleic acid for a transcript of a syntaxin gene and / or the syntaxin 12 gene, or a portion thereof; and (c) a nucleic acid construct that generates (a) or (b) in a cell. Also disclosed is a method for controlling spider mites belonging to the family Tetranychidae, the method comprising a step for applying any of the following (a) to (c): (a) a double-stranded RNA that has an RNAi effect on syntaxin genes and / or the syntaxin12 gene; (b) an antisense nucleic acid for a transcript of a syntaxin gene and / or the syntaxin 12 gene, or a portion thereof; and (c) a nucleic acid construct that generates (a) or (b) in a cell.

The invention discloses an anti-degradation antisense nucleic acid based on a D-type DNA structure and a preparation method and application thereof, and belongs to the technical field of genetic engineering. Compared with the traditional antisense nucleic acid, the anti-degradation antisense nucleic acid (D-ASO) based on the D-type DNA structure has the advantages that the design of coupling a single-chain string and a double-chain bow is adopted, the nuclease degradation resistance is remarkably improved, and the half-life period in serum is prolonged to 24 hours (only 2 hours in the traditional ASO). The target mRNA triggers the replacement of a protection chain (P) of D-ASO to form a DNA-RNA hybrid which is degraded by RNase H, and then the P chain is recombined to realize cyclic utilization (more than or equal to 5 times). According to the innovative structure, the binding rate of non-specific RNA is reduced by 90% or above. The invention solves the problems of stability and off-target toxicity of ASO while maintaining efficient gene silencing, and is suitable for treatment of tumors and genetic diseases.

The present application relates to a kind of drug delivery system based on nucleic acid chemical modification and its preparation method and application.The drug delivery system includes nucleic acid aptamer coupling drug and antisense nucleic acid coupling drug, and the nucleic acid aptamer coupling drug and antisense nucleic acid coupling drug are co-assembled to form nanoparticle;The nucleic acid aptamer coupling drug includes nucleic acid aptamer and the chemotherapeutic drug coupled therewith;The antisense nucleic acid coupling drug includes antisense nucleic acid and the photosensitizer coupled therewith.The present application can reduce the up-regulation of the expression level of anti-apoptotic gene caused by chemotherapy and photodynamic therapy in tumor site by assembling tumor-targeting nucleic acid aptamer, chemotherapeutic drug, photosensitizer and antisense nucleic acid into drug delivery system, realizes the combination of chemotherapy, photodynamic therapy and gene therapy, efficiently inhibits tumor growth, and preparation method is simple and easy to operate, with universality, large drug loading, high production efficiency, it is expected to be applied in the treatment of various diseases, and promote the popularization and use of related products.

The present invention provides an inhibitor capable of inhibiting the expression of PCDHA11 and inhibiting the function of PCDHA11. Specifically, the present invention provides nucleic acid molecules such as siRNA or antisense nucleic acids that inhibit PCDHA11 expression. These inhibitors are effective against gastric cancer, pancreatic cancer, breast cancer, esophageal squamous cell carcinoma, lung adenocarcinoma, colon cancer, and the like, and can be used as pan-cancer therapeutics.

A double-stranded nucleic acid-galactosamine-cholesterol compound and a use thereof, relating to the technical field of nucleic acid drugs. The double-stranded nucleic acid-galactosamine-cholesterol compound is composed of a double-stranded nucleic acid, galactosamine, and cholesterol which are linked in sequence; the double-stranded nucleic acid is a double-stranded nucleic acid capable of inhibiting the transcription level and / or expression level of a target gene, and is composed of an antisense nucleic acid strand and a complementary strand; the galactosamine is linked to the 5' end of the complementary strand of the double-stranded nucleic acid. Also provided is a use of the double-stranded nucleic acid-galactosamine-cholesterol compound in the preparation of a drug having the effect of inhibiting the transcription level and / or expression level of a target gene and having a protective effect on the kidney. The double-stranded nucleic acid-galactosamine-cholesterol compound can cross the blood-brain barrier and can significantly reduce the renal burden, providing a technical platform for the treatment of refractory neurological diseases such as Alzheimer's disease and Parkinson's disease.

The present invention provides an antisense nucleic acid, a splicing promoter, and a pharmaceutical composition that improve TDP-43 exitron splicing anomalies, that can effectively suppress a decrease in function of TDP-43 in nuclei which occurs along with the accumulation of TDP-43 anomalies, and that can be applied to the treatment of neurodegenerative disease. Provided is an antisense nucleic acid for which a target sequence is position 760 onward in the base sequence represented by SEQ ID NO: 1, which includes a base sequence having complementarity with a sequence comprising not less than 10 consecutive bases in the target sequence, and which promotes TDP-43 splicing. Also provided are a splicing promoter and a pharmaceutical composition which comprise the same.

In one aspect, the invention provides a method of screening a human subject to determine if said subject has a genetic predisposition to develop, or is suffering from Facioscapulohumeral Dystrophy (FSHD), said method comprising: (a) providing a biological sample comprising genomic DNA from the subject; and (b) analyzing the portion of the genomic DNA in the sample corresponding to the distal D4Z4-pLAM region on chromosome 4 and determining the presence or absence of a polymorphism resulting in a functional polyadenylation sequence operationally linked to exon 3 of the DUX4 gene.

The application discloses an oligonucleotide drug preparation applied to liver cancer treatment and a preparation method and application thereof. The drug preparation is composed of an oligonucleotide drug, a carrier and a solvent, wherein the oligonucleotide drug is PHN02 ME , the oligonucleotide drug PHN02 ME adopts 5 cap modifications at two ends on the basis of a full thio sequence, and the carrier is composed of nucleotide phospholipid TPS or CPS, cationic lipid CLDA and auxiliary lipid DSPE-PEG. The application obtains a new liver cancer resistant drug preparation with great clinical application potential through preparation proportion adjustment and preparation solvent optimization. After low-dose and low-frequency intravenous administration of the preparation to mice, the growth of liver cancer in the mice is significantly inhibited, and the preparation shows ideal sustained release / long-acting anticancer effect, and the drug efficacy is better than that of a CT102 / DNCA / CLD / PEG preparation. The application lays a foundation for the wide clinical application of the liver cancer resistant antisense nucleic acid drug, and also has wide application prospects in the field of gene therapy.

Provided is an oligonucleotide conjugate comprising an oligonucleotide and two or more linearly connected asialoglycoprotein receptor-binding molecules attached to the oligonucleotide, wherein the oligonucleotide comprises a locked nucleoside analog having a bridging structure between the 4′ and 2′ positions, is complementary to a human PCSK9 gene, and has inhibitory activity on the expression of the human PCSK9 gene. The oligonucleotide conjugate of the present invention can be used in the field of pharmaceutical products, in particular, the field of the development and production of therapeutic agents for diseases associated with a high LDL cholesterol level.

To provide an agent for highly efficiently skipping the 51st exon of a human dystrophin gene in the treatment of Duchenne muscular dystrophy (DMD).SOLUTION: The following (a1) to (d1): (a1) an antisense oligomer comprising a specific nucleotide sequence; (b1) an antisense oligomer comprising a nucleotide sequence derived from the specific nucleotide sequence by deletion, substitution, insertion, and / or addition of 1 to 5 nucleotides; (c1) an antisense oligomer comprising a nucleotide sequence derived from the specific nucleotide sequence by deletion, substitution, insertion, and / or addition of 1 to 5 nucleotides; An antisense oligomer comprising a base sequence having a sequence identity of 80% or more; and (d1) an antisense oligomer hybridizing under stringent conditions with an oligonucleotide consisting of a base sequence complementary to a specific base sequence, provided that the specific base sequence is excluded, or a pharmaceutically acceptable salt thereof or a hydrate thereof.SELECTED DRAWING: None

The present invention discloses, for example, a control agent for spider mites belonging to the family Tetranychidae, the control agent comprising any of (a) to (c) below: (a) a double-stranded RNA having an RNAi effect on a syntaxin gene and / or a syntaxin-12 gene; (b) an antisense nucleic acid against a transcript of a syntaxin gene and / or a syntaxin-12 gene, or a part thereof; and (c) a nucleic acid construct that intracellularly produces (a) or (b); a method for controlling spider mites belonging to the family Tetranychidae, the method comprising a step that involves application of any of (a) to (c) below: (a) a double-stranded RNA having an RNAi effect on a syntaxin gene and / or a syntaxin-12 gene; (b) an antisense nucleic acid against a transcript of a syntaxin gene and / or a syntaxin-12 gene, or a part thereof; and (c) a nucleic acid construct that intracellularly produces (a) or (b); and the like.