54 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.

To provide a technique capable of recovering a normal Fukutin protein.SOLUTION: An antisense nucleic acid is a morpholino oligomer in which a range of position 2044 to position 2068 of a base sequence shown by sequence number 1 is used as a target sequence, any consists of one base sequence of the following (a) to (c): (a) a base sequence expressed by sequence number 2 or sequence number 3; (b) a base sequence having 90% or higher identity with the base sequence expressed by sequence number 2 or sequence number 3; and (c) a base sequence in which one or several bases are deleted, substituted or added in the base sequence expressed by sequence number 2 or sequence number 3.SELECTED DRAWING: Figure 14

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 method for constructing a low-copy plasmid production strain and its application, and relates to the field of genetic engineering technology. The present invention, through directed transformation of E. coli JM109 (DE3) strain, uses CRISPR / Cas9 gene editing technology, inserts the antisense nucleic acid anti-rop of the rop gene into the fhuA gene, and uses the artificial promoter J23119 (SpeI) promoter to start transcription, the extraction rate of the PET series plasmid can be increased from 4.4% (plasmid extraction amount / thalline wet weight) to 20.6%, and the plasmid copy number is increased from 1 / 10 of the normal CoIE1 type plasmid to 1 / 2 of the normal CoIE1 type plasmid, which can greatly improve the efficiency of genetic engineering experiments, promote research progress in related fields, and provide new possibilities and technical support for the industrial production of plasmids.

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.

To provide improved methods and compositions for treating cancers using antisense.SOLUTION: The present disclosure relates to compositions and methods for treating cancers using antisense (AS) nucleic acids directed against Insulin-like Growth Factor 1 Receptor (IGF-1R). The AS may be administered to the patients systemically, or may be used to produce an autologous cancer cell vaccine. The AS is 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 cancer, e.g., glioblastoma.SELECTED DRAWING: None

The invention provides a Mena antisense oligonucleotide and a preparation method of the Mena antisense oligonucleotide. The antisense oligonucleotide is antisense oligonucleotide targeting a Mena gene core sequence, five antisense nucleic acids are analyzed in a wisdom gene database, and it is found that no sequence identical to the antisense nucleic acid target sequence exists, so that the four antisense nucleic acids do not generate an off-target effect. The ASO-Mena can be used for effectively inhibiting the scratch healing speed of lung cancer cells. The ASO-Mena1, 2 can inhibit lung cancer cell metastasis, and almost has no toxic influence on normal cells.

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 invention provides a small activating RNA (Ribonucleic Acid) which consists of a sense oligonucleotide chain and an antisense oligonucleotide chain and is used for activating or up-regulating human p21 gene expression, and the sense oligonucleotide chain or the antisense oligonucleotide chain has more than 75% of homology with any continuous fragment with the length of 16-35 nucleotides in a target gene sequence of a human p21 gene promoter. Wherein the target sequence of the human p21 gene is selected from a group consisting of sequences as shown in SEQ ID NO: 5, 6, 7, 8, 9, 10, 11 and 12.

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

This application provides antisense nucleic acid compounds that reduce UBE3A mRNA levels and / or UBE3A polypeptide levels in central nervous system neurons, thereby alleviating effects and symptoms caused by excess UBE3A levels. The application further provides compositions comprising antisense nucleic acid compounds and their use in methods of preventing or treating conditions associated with excess UBE3A mRNA and / or UBE3A polypeptide levels in a subject.

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.

Provided herein are antisense nucleic acids that targets a 5' upstream open reading frame of an ABCD2 mRNA, wherein the antisense nucleic acid comprises a phosphorodiamidate morpholino backbone. Also provided herein are methods of treating adrenoleukodystrophy (ALD) in a subject in need thereof, the method including administering a therapeutic agent to the subject, wherein the therapeutic agent increases ABCD2 gene expression, thereby treating ALD.

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 relates to an isolated antisense molecule capable of inhibiting expression of the LMNA gene in a mammalian cell, the antisense molecule comprising an antisense nucleic acid strand that is substantially complementary to a target region of a transcript encoded by the LMNA gene, the antisense nucleic acid strand being at least complementary to SNP rs538089, rs505058, or rs4641 in the target region.

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 provides a highly functional antisense oligonucleotide that inhibits biosynthesis of chondroitin sulfate. The invention also provides an antisense oligonucleotide that suppresses expression of the chondroitin sulfate N-acetylgalactosaminyl-transferase-1 (CSGalNAc-T1) gene and has the properties (i) to (iv): (i) an antisense oligonucleotide is 13- to 25-mer in length; (ii) an antisense oligonucleotide comprises a gap region, a 3′-wing region bound to the 3′ end of the gap region, and a 5′-wing region bound to the 5′ end of the gap region; (iii) nucleotides in the 3′-wing region and in the 5′-wing region include at least one bridged nucleic acid and the bridged nucleic acid is scpBNA or AmNA; and (iv) an antisense oligonucleotide comprises a nucleotide sequence selected from the group consisting of SEQ ID NOs: 2 to 31 or a sequence derived therefrom by substitution, deletion, or insertion of 1 or 2 nucleic acid bases.

An antitumor agent according to the present disclosure contains, as an active ingredient, at least one component selected from the group consisting of ribozyme nucleic acids, antisense nucleic acids, RNAi-inducing nucleic acids, dominant negative variants, and aptamers, and vectors that express the same.

A lipid nanoparticle and a preparation method and use thereof are provided. The lipid nanoparticle (LNP) includes a carrier and an encapsulated nucleic acid, the carrier includes an ionizable lipid, a helper phospholipid, a PEGylated lipid, cholesterol and its derivatives, and a retinoid compound; and the nucleic acid is one or more of mRNA, circRNA, siRNA, microRNA, antisense nucleic acid, and plasmid.

The invention provides antisense nucleic acid of a targeted KRAS gene as well as a pharmaceutical preparation and application of the antisense nucleic acid, and belongs to the technical field of biological medicines. The nucleotide sequence of the antisense nucleic acid provided by the invention is as shown in 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 as shown in SEQ ID NO: 1 and a modified nucleotide sequence as shown in SEQ ID NO: 8. The antisense nucleic acid can target a 3 '-UTR region of mRNA of KRAS, down-regulate corresponding mRNA and various mutants of the mRNA and inhibit growth of tumor cells, a pharmaceutical preparation of the antisense nucleic acid can deliver the target antisense nucleic acid to a tumor site and exert a remarkable inhibition effect, and the antisense nucleic acid has huge application potential in the field of tumor gene therapy of KRAS mutation.

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.

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

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.