91 results about "Exon skipping" 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 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 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 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.

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 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.

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.

Antisense oligomers complementary to a selected target site in the human dystrophin gene to induce exon 51 skipping are described.

To provide exon-skipping oligomer conjugates for muscular dystrophy.SOLUTION: Disclosed is an antisense oligomer conjugate that is complementary to a selected target site of the human dystrophin gene and induces exon 45 skipping. The disclosure relates to a novel antisense oligomer conjugate suitable for exon 45 skipping of the human dystrophin gene and a pharmaceutical composition thereof. The disclosure also provides a method for inducing exon 45 skipping using the novel antisense oligomer conjugate, a method for enabling a subject having a mutation of the dystrophin gene that is amenable to exon 45 skipping to produce dystrophin, and a method for treating a subject having a mutation of the dystrophin gene amenable to exon 45 skipping.SELECTED DRAWING: None

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.

Disclosed herein are antibody-oligonucleotide conjugates and pharmaceutical compositions comprising the antibody-oligonucleotide conjugates that induce an alteration in an incorrectly spliced dystrophin mRNA transcript to induce DMD exon 52 skipping. Also described herein include methods for treating muscle dystrophy including Duchenne muscular dystrophy by administering antibody-oligonucleotide conjugates or a pharmaceutical composition comprising the antibody-oligonucleotide conjugates that induce an alteration in an incorrectly spliced dystrophin mRNA transcript to induce DMD exon 52 skipping.

The present invention relates to the treatment of subjects with cancers that have c-Met exon 14 skipping mutations.

The present invention provides a mesenchymal stem cell having blood compatibility, and a preparation method and use thereof, the mesenchymal stem cell inducing exon skipping of an exon 5 by performing gene modification on the exon 5 of an F3 gene, thereby increasing the expression of a selective splicing tissue factor (asTF), and improving the blood compatibility of the mesenchymal stem cell. The present invention relates to a method for inhibiting thrombosis by reducing or inhibiting the expression or activity level of a full-length tissue factor (flTF), which is a blood coagulation promoter, and thereby inhibiting thrombosis.

The present application relates to the technical field of gene mutation detection, and particularly relates to a system, method and application for detecting exon skipping mutation.The present application constructs a self-catalytic system based on specific double recognition induction of CRISPR-Cas12a, which is used for sensitive and reliable detection of MET 14 exon skipping mutation of lung cancer patients.The system can effectively release the fluorescence signal through the Cas12a auxiliary cutting, and further realize signal amplification through the self-catalytic mechanism.The present application can solve the technical problems of the existing exon skipping mutation detection system, such as complex detection process, long time consumption, and unsatisfactory detection accuracy.The detection system of the present application has high sensitivity, stability and good reproducibility, and the method has low cost, simple operation, short detection period, good specificity, and low false positive rate and false negative rate.The present application is suitable for clinical sample determination and has an ideal application prospect.

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.

Disclosed herein are oligonucleotide conjugates and pharmaceutical compositions for inducing multi-exon skipping. In some instances, also disclosed herein are methods of treating a muscular dystrophy, including treating Duchenne muscular dystrophy or Becker muscular dystrophy.

Antisense polynucleotides and their use in pharmaceutical compositions to induce exon skipping in targeted exons of the gamma sarcoglycan gene are provided, along with methods of preventing or treating dystrophic diseases such as Limb-Girdle Muscular Dystrophy.

The present invention relates to a modified U1 snRNA configured to rescue exon skipping in a mutant ABCA4 gene. In one aspect of the invention, there is provided a modified U1 small nuclear RNA (snRNA) configured to retain exon 40 in a mature mRNA transcript of a mutant ABCA4 gene comprising a mutation that induces exon 40 skipping wherein the mutation is located between 3 base pairs upstream and 8 base pairs downstream of a donor splice site of exon 40, wherein the modification comprises replacing a portion of the single-stranded nucleotide sequence of the 5'region of the wild-type U1 snRNA with a single-stranded binding nucleotide sequence capable of hybridizing to a target sequence present on the precursor mRNA transcript of the mutant ABCA4 gene, and wherein the target sequence is located in a region between 13 base pairs upstream and 15 base pairs downstream of the donor splice site of exon 40. In another aspect, there is provided a nucleic acid construct comprising a polynucleotide sequence encoding a modified U1 snRNA as described herein.

Antisense oligomer conjugates complementary to a selected target site in the human dystrophin gene for inducing exon 45 skipping are described.

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.

The invention relates to the fields of medicine and biotechnology. In particular, it relates to novel antisense oligonucleotides (AONs) that may be used in the treatment, prevention and / or delay of Stargardt disease and / or ABCA4-associated eye disease. More in particular, the invention relates to AONs that are used in inhibiting or blocking exon 39 skipping in the human ABCA4 pre-mRNA.

Disclosed herein are methods of identifying a guide RNA (gRNA) that induces exon skipping in a target gene. Also disclosed are methods of inducing exon skipping in a target gene methods of controlling heterogeneity of a phenotypic outcome.

The present application provides a method of inducing precursor mRNA exon skipping in a host cell comprising introducing into the host cell a deaminase recruitment RNA (dRNA) or a construct comprising a nucleic acid encoding the dRNA wherein the dRNA is a circular RNA (circRNA) or forms a circular RNA in the host cell.

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.

The present invention relates to antisense oligonucleotides (ASO) for use in treating, preventing, or ameliorating the progression of conditions such as type 2 diabetes mellitus (T2DM) and insulin resistance, leptin resistance, and obesity, Rater Syndrome, and cancer. Specifically, a thiomorpholino-containing ASO targets a protein tyrosine phosphatase non-receptor type 1 (PTPN1) gene transcript and induces exon skipping (including exon 2) of the transcript during RNA processing, thereby inhibiting expression of the protein tyrosine phosphatase-1B (PTP1B) protein.

Among other things, the present disclosure provides oligonucleotide compositions and methods thereof. In some embodiments, oligonucleotides comprise various chemical modifications of sugars, nucleobases, and / or mtemucleotidic linkages and patterns thereof and are useful for exon skipping. In some embodiments, the present disclosure provides technologies useful for skipping exon 45 of dystrophin (DMD) transcripts. In some embodiments, the present disclosure provides technologies useful for modulating DMD transcript splicing. In some embodiments, the present disclosure provides methods for preventing or treating conditions, disorders or diseases including Duchenne muscular dystrophy.

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.

Disclosed herein are antibody-oligonucleotide conjugates and pharmaceutical compositions comprising the antibody-oligonucleotide conjugates that induce an alteration in an incorrectly spliced dystrophin mRNA transcript to induce DMD exon 50 skipping. Also described herein include methods for treating muscle dystrophy including Duchenne muscular dystrophy by administering antibody-oligonucleotide conjugates or a pharmaceutical composition comprising the antibody-oligonucleotide conjugates that induce an alteration in an incorrectly spliced dystrophin mRNA transcript to induce DMD exon 50 skipping.

The disclosure relates to the field of chronic pain and the treatment thereof. The disclosure involves antisense oligonucleotides and the use thereof in pre-mRNA and mRNA modulation, in one aspect related to RNA editing using endogenous ADAR enzymes, in targeting an adenosine in a (pre-) mRNA for human Nav1.7, preferably to change from a lysine residue to an arginine residue in the protein at position 1406 (K1406R), thereby impairing the ability of the Nav1.7 protein to act as a sodium ion channel. In another aspect the disclosure relates to exon skipping wherein antisense oligonucleotides are used to induce skipping of exon 23 in the generation of human SCN9A mRNA thereby generating a shortened Nav1.7 protein with an impaired ability to act as a sodium ion channel. The disclosure relates to methods and means to alter the Nav1.7 protein in cells of the peripheral nervous system, preferably large nociceptor cells (type Aα / Aβ), to provide a treatment of chronic pain.