452results about "Splicing alteration" patented technology

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

Aspects of the disclosure relate to complexes and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such complexes comprising an oligonucleotide (e.g., useful for targeting DMPK) covalently linked to an antibody (e.g., anti-TfR1 antibody).

Aspects of the disclosure relate to complexes and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such complexes comprising an oligonucleotide (e.g., useful for targeting DMPK) covalently linked to an antibody (e.g., anti-TfR1 antibody).

Disclosed herein are molecules and pharmaceutical compositions that induce an insertion, deletion, duplication, or alteration in an incorrectly spliced mRNA transcript to induce exon skipping or exon inclusion. Also described herein include methods for treating a disease or disorder that comprises a molecule or a pharmaceutical composition that induces an insertion, deletion, duplication, or alteration in an incorrectly spliced mRNA transcript to induce exon skipping or exon inclusion.

Aspects of the disclosure relate to complexes and other aspects relate to formulations (e.g., aqueous, lyophilized forms) comprising such complexes comprising an oligonucleotide (e.g., useful for targeting DMPK) covalently linked to an antibody (e.g., anti-TfR1 antibody).

Antisense oligonucleotides for splicing modulation of UNC13A (e.g., inhibiting inclusion of an UNC13A cryptic exon into an UNC13A mature mRNA), compositions including the antisense oligonucleotides, and methods of use are described. Also disclosed are pharmaceutical compositions including one or more antisense oligonucleotides and methods of treating an UNC13A-associated disease or a disease associated with TDP-43 dysfunction in a subject by administering the antisense oligonucleotides to the subject.

Aspects of the present disclosure relate to conjugates comprising a muscle targeting agent covalently linked to a molecular payload. In some embodiments, the muscle targeting agent specifically binds to an internalized cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in mRNA expressed from a mutant DMD allele.

The invention relates to guide polynucleotides and methods for targeting and editing a portion of the 5' UTR-encoding region of genes encoding VGSC alpha subunits (NaV) to abrogate or create an upstream open reading frame (uORF). The invention relates to guide polynucleotides and methods for targeting and editing a portion of the 5' splice acceptor site (SA) of an exon of a gene encoding a voltage-gated sodium channel (VGSC) alpha subunit (NaV). The invention also relates to use of the guide polynucleotides and methods for treating genetic disorders, in particular Dravet syndrome.

Disclosed herein are antibody oligonucleotide conjugates and pharmaceutical compositions that induce an alteration in an incorrectly spliced dystrophin mRNA transcript to induce exon 44 skipping. Also described herein include methods for treating muscle dystrophy including Duchenne muscular dystrophy that comprises administering antibody oligonucleotide conjugates or a pharmaceutical composition that induces alteration in an incorrectly spliced dystrophin mRNA transcript to induce exon 44 skipping.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

To provide antisense oligonucleotide sequences and methods of using the same for treating neurological diseases.SOLUTION: Provided is an oligonucleotide comprising linked nucleosides having a sequence of at least 19 contiguous nucleobases, wherein the sequence of nucleobases comprises a portion of at least 10 contiguous nucleobases that is at least 90% complementary to an equal length portion of nucleobases contained at a specified position of a specified sequence.SELECTED DRAWING: Figure 1A

This invention relates to oligonucleotide compositions and methods for using the same. [Solution] In particular, this disclosure provides designed oligonucleotides, compositions thereof and methods of use. In some embodiments, this disclosure provides techniques useful for reducing transcript levels. In some embodiments, this disclosure provides techniques useful for modulating transcript splicing. In some embodiments, the techniques provided can alter the splicing of dystrophin (DMD) transcripts. In some embodiments, this disclosure provides methods for treating diseases such as Duchenne muscular dystrophy and Becker muscular dystrophy.

A method for inhibiting aberrant splicing in a Stathmin-2 (STMN2) transcript, the method comprising: genetically editing a STMN2 gene in a cell to delete (a) one or more nucleotides in a 3' splice site of intron 1, wherein the 3' splice site is adjacent to exon 2a, (b) one or more nucleotides in a region of intron 1 that is adjacent to the 3' splice site, or both (a) and (b), thereby inhibiting production of STMN2 transcripts including exon 2a and improving production of functional STMN2 transcripts in the cell. Also provided herein are gene editing systems for genetic modification of the STMN2 gene.

The present invention relates to a recombinant antisense oligonucleotide that targets CD33 mRNA and to a method of preparing a substantially pure population of edited eukaryotic cells comprising the steps of i) editing a population of eukaryotic cells by the use of base editors, (ii) treating the same population with antisense oligonucleotides according to the invention to transiently downregulate CD33 and iii) enriching the population of edited eukaryotic cells that is negative for CD33.

Antisense oligonucleotides for modulating UNC13A splicing (e.g., inhibiting the inclusion of UNC13A hidden exons in mature UNC13A mRNA), compositions comprising such antisense oligonucleotides, and methods of use are described. Also disclosed are pharmaceutical compositions comprising one or more antisense oligonucleotides, and methods for treating UNC13A-related diseases or diseases associated with TDP-43 dysfunction in a subject by administering the antisense oligonucleotides to that subject.

The present application provides an engineered circular RNA capable of recruiting adenosine deaminase acting on RNA (ADAR; arRNA) and its application in treating Duchenne muscular dystrophy (DMD).

An isolated or purified AON for modifying pre-mRNA splicing in the Receptor for Advanced Glycation End-products (RAGE) to modulate splicing of the RAGE gene transcript or part thereof is provided.

Hereditary peripheral neuropathy, also known as Charcot-Marie-Tooth disease (CMT), is one of the most common genetic disorders of the nervous system, affecting approximately 1 in 2500 people. The present disclosure relates to a therapeutic strategy, including methods and compositions, for treating Charcot-Marie-Tooth disease (CMT) by targeting the pre-mRNA of PMP22 using antisense oligonucleotides (ASOs).

Disclosed are conjugates of an oligonucleotide and a peptide covalently bonded or linked to the oligonucleotide via a linker that target a human dystrophin gene, compositions including the same, and methods of use thereof.

The disclosure relates to the field of gene therapy for the treatment of an osteosarcoma using splice-switching oligonucleotides. Increased expression of INSR-A, an isoform frequently expressed in cancer, can effectively evade current therapeutic mechanisms and contribute to resistance in cancer patients. As a means to address the ability of cancer to evade therapies through this mechanism, Applicant provides a polynucleotide comprising a promoter, for example a U7 or a U1 promoter, and a first splice-switching oligonucleotide (SSO) that targets a regulatory element of an insulin receptor (JR).

We provide gene therapy for the treatment of muscular dystrophy, including but not limited to Duchenne muscular dystrophy (DMD). [Solution] This disclosure provides a recombinant adeno-associated virus (rAAV) comprising a nucleic acid molecule that delivers a nucleic acid encoding a U7-based snRNA, which is a nucleic acid that induces exon skipping for use in the treatment of muscular dystrophy, including but not limited to DMD, resulting from any mutation suitable for skipping exon 44 of the DMD gene (DMD exon 44), including but not limited to mutations involved in or affecting DMD exon 44.

To provide a nucleic acid trans-splicing molecule that can replace an exon in a targeted mammalian ocular gene carrying a defect or mutation causing an ocular disease with an exon having the naturally-occurring sequence without the defect or mutation.SOLUTION: Disclosed is an RNA trans-splicing molecule useful for the treatment of diseases caused by the deletion of one or more exons of a coding sequence. The trans-splicing molecule includes a 3' transcription terminator domain that enhances the efficiency of trans-splicing. The 3' TTD comprises a triple helix domain and a tRNA-like domain.SELECTED DRAWING: None

HTT nucleic acid trans-splicing molecules are described, which include a coding domain containing one or more exons of HTT, a splice site, and a binding domain that binds to a target intron of HTT pre-mRNA. The HTT nucleic acid trans-splicing molecules described herein can also be used in combination with, for example, an MSH3-binding domain arranged in tandem with an HTT-binding domain, an MSH3 nucleic acid trans-splicing molecule, an MSH3 splice modulator, an antisense oligonucleotide or antisense RNA against either MSH3 or HTT, and an MSH3 or HTT microRNA (miRNA), as well as constructs encoding them. Compositions containing the nucleic acid trans-splicing molecules described herein also encompass compositions containing a combination of the nucleic acid trans-splicing molecule and an additional therapeutic agent (e.g., an MSH3 nucleic acid trans-splicing molecule, an MSH3 splice modulator, an antisense oligonucleotide or antisense RNA against either MSH3 or HTT). Nucleic acid trans-splicing molecules and compositions containing them can be used alone or in combination with additional therapeutic agents in methods for treating Huntington's disease (HD). Also described herein are nucleic acid trans-splicing molecules for use alone or in combination with additional therapeutic agents in the treatment of HD or in the preparation of a medicament for treating HD. Also included herein are MSH3 nucleic acid trans-splicing molecules, MSH3 splice modulators, and MSH3 miRNAs, and constructs encoding them, which may be used alone or in combination and / or in combination with additional therapeutic agents to treat a nucleotide repeat disorder (e.g., HD) or in the preparation of a medicament for treating a nucleotide repeat disorder (e.g., HD).

Described herein in various embodiments are compositions comprising (a) a cyclic peptide; and (b) an antisense compound, wherein the antisense compound targets exon 44 of the DMD gene in a pre-mRNA sequence.

The application provides an antisense oligonucleotide Jag-i9 ASO and application thereof, relates to the technical field of biological medicine, and the antisense oligonucleotide Jag-i9 ASO has the sequence of 5'-ACTGGGCCCTGCACCTGA-3'. By providing the antisense oligonucleotide of a specific sequence, the binding site of target heterogeneous ribonucleoprotein K and the Jag2 gene is targeted, the expression of the pro-inflammatory Jag2 subtype is inhibited, the Jag2 gene splicing site can be accurately targeted, the heterogeneous ribonucleoprotein K binding function is specifically blocked, a targeted intervention means is provided for the treatment of myocardial ischemia-reperfusion injury, the generation of the pro-inflammatory subtype is inhibited by efficiently and accurately regulating the alternative splicing of a specific gene, myocardial cell apoptosis and inflammatory response are reduced, myocardial function is improved, and a new approach is provided for the prevention and treatment of myocardial ischemia-reperfusion injury, the treatment effect is improved, and the advantages of reducing side effects are achieved.

SnRNA systems targeting GAA and GYS1 RNA sequences, and polynucleotides and vectors comprising the same, are disclosed herein. Further disclosed are methods of treating Pompe disease, e.g., using such RNA sequences, polynucleotides and vectors.

Disclosed herein are CRISPR-free compositions and methods for producing chimeric RNA molecules via trans-splicing, and methods for treating and / or preventing genetic diseases or disorders using the chimeric RNA molecules produced via trans-splicing. Disclosed herein are nucleic acid molecules comprising exogenous RNA to be trans-spliced ​​into a target endogenous pre-mRNA, a 5' hemi-intron, one or more RNA targeting motifs, and one or more RNA structures.