45 results about "Dystrophin" patented technology

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.

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.

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.

The present invention relates to medium-sized muscular dystrophin comprising at least the rod-like domains R1, R8, R9, R10, R11, R12, R16, R17 and R24 of the muscular dystrophin, and their use in the treatment of muscular dystrophy, in particular Duchenne muscular dystrophy (DMD).

Provided herein are dual adeno-associated virus (AAV) particle compositions for delivering a mid-length dystrophin coding sequence over two AAV vectors resulting in reconstitution of mid-length dystrophin protein in a cell. This method results in the expression of a larger dystrophin protein that cannot be expressed using a traditional single AAV strategy. Such methods can be used for the treatment of Duchenne muscular dystrophy.

The invention described herein provides a method of treatment for a disease in a human in need thereof, comprising administering to the human an rAAV viral particle comprising a polynucleotide encoding a therapeutic gene-of-interest, as described herein. The method can be used for delivering a gene of interest (GOI), such as a microdystrophin-encoding polynucleotide sequence, for the treatment of a disease, e.g., muscular dystrophy such as Duchenne muscular dystrophy (DMD).

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.

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.

The present disclosure provides methods and compositions concerning the disclosed genetic constructs, including those that target mutated portions of a dystrophin gene for excision, thereby restoring functional dystrophin protein expression. The disclosure further provides methods and compositions for treating Duchenne muscular dystrophy.

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 disclosure covers engineered macronucleases that bind to and cleave recognition sequences within the dystrophin gene. This disclosure also covers methods for preparing genetically modified cells using such engineered macronucleases. Furthermore, this disclosure covers pharmaceutical compositions comprising engineered macronuclease proteins or polynucleotides encoding engineered macronucleases of this disclosure, and the use of such compositions for modifying the dystrophin gene in a subject or for treating Duchenne muscular dystrophy.

The present disclosure provides compositions related to the selective binding of both endogenous dystrophin proteins (e.g., full length dystrophin), which are relevant for their role in numerous genetic neuromuscular disorders, including Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), and microdystrophin proteins (e.g., delandistrogene moxeparvovec-rokl), which are used in the treatment of genetic neuromuscular disorders. The disclosure includes proteins, antibodies and / or fragments thereof and associated polynucleotide constructs. The disclosure further provides methods for manufacturing said compositions and other uses for the same.

Nucleotide sequences including a micro-dystrophin gene are provided. The micro-dystrophin genes may be operatively linked to a regulatory cassette. Methods of treating a subject having, or at risk of developing, muscular dystrophy, sarcopenia, heart disease, or cachexia are also provided. The methods may include administering a pharmaceutical composition including the micro-dystrophin gene and a delivery vehicle to a subject. Further, the methods may include administering the pharmaceutical composition a subject having Duchenne muscular dystrophy or Becker muscular dystrophy.

Embodiments of the disclosure include methods and compositions for the renewal of cardiomyocytes by targeting the Hippo pathway. In particular embodiments, an individual with a need for cardiomyocyte renewal is provided an effective amount of a shRNA molecule that targets the Sav1 gene. Particular shRNA sequences are disclosed.

To provide an AAV vector encoding micro - or mini-dystrophin that is expressed at effective levels in transduced cells of a subject having DMD or BMD, and is preferably capable of minimizing an immune response to a therapeutic protein.SOLUTION: Provided are inventions based, in part, on novel genetic constructs encoding micro-dystrophin proteins for use in gene therapy. The micro-dystrophin gene constructs and expression cassettes were designed to result in improved therapies with respect to efficacy, potency, and safety for subjects when expressed by viral vectors in muscle cells and / or CNS cells.SELECTED DRAWING: Figure 1A

The invention provides for recombinant AAV vectors comprising a a miniaturized human micro-dystrophin gene and methods of using the recombinant vectors to reduce or prevent fibrosis in subjects suffering from muscular dystrophy.

This disclosure provides, in particular, oligonucleotide compositions and methods thereof. In some embodiments, the oligonucleotides comprise various chemical modifications of sugars, nucleobases, and / or internucleotide bonds and their patterns, and are available for exon skipping. In some embodiments, this disclosure provides techniques for use with exon 51 of a jumping dystrophin (DMD) transcript. In some embodiments, this disclosure provides techniques for modulating DMD transcript splicing. In some embodiments, this disclosure provides methods for preventing or treating conditions, disorders, or diseases including Duchenne muscular dystrophy.

Disclosed herein are nucleic acid molecules, polypeptides, cells, vectors, and pharmaceutical compositions relating to miniaturized dystrophin. Methods of production and methods of therapeutic use of the miniaturized dystrophin are also disclosed.

To provide adeno-associated virus vector delivery of micro-dystrophin to treat muscular dystrophy.SOLUTION: The invention provides recombinant AAV vectors comprising a miniaturized human micro-dystrophin gene, and methods of using the recombinant vectors to reduce or prevent fibrosis in subjects suffering from muscular dystrophy. The present invention is directed to gene therapy methods that directly reduce the three primary components of connective tissue (collagen 1, collagen 3 and fibronectin) by delivering the microRNA miR29. In this system, the miR29 binds to the 3' UTR of the collagen and fibronectin gene to down-regulate expression. The invention is directed to gene therapy vectors, e.g., AAV, expressing the guide strand of the microRNA miR29, and a method of delivering miR29 to the muscle to reduce and / or prevent fibrosis.SELECTED DRAWING: None

FIELD: biotechnology.SUBSTANCE: method for producing a recombinant adeno-associated virus (rAAV) rAAVrh74.MHCK7.microdystrophin in adherent mammalian cells by propagating cells in a hybrid seed bioreactor system is described, comprising: (a) culturing adherent cells under adherent conditions with a first growth medium containing serum in container N-2; (b) removing adherent cells from the first medium; (c) inoculating adherent cells from step (b) into a second medium that does not contain serum or contains serum at a concentration lower than in the first medium in container N-1; (d) culturing adherent cells in container N-1 under suspension conditions; (e) inoculating adherent cells from step (d) into a third medium in a bioreactor for growing adherent cultures; and (f) transfecting the adherent cells with a transgenic plasmid containing the rAAVrh74.MHCK7.microdystrophin construct, a plasmid containing the AAV rep gene and the AAV cap gene, and an adenoviral helper plasmid, to produce rAAV containing the human microdystrophin nucleotide sequence of SEQ ID NO:1 and the MHCK7 promoter sequence of SEQ ID NO: 7.EFFECT: expanding the scope of treatments for muscular dystrophy.18 cl, 8 tbl, 11 ex

The present disclosure provides gene therapy vectors, such as recombinant adeno-associated virus (rAAV) for expressing a human micro-dystrophin gene. The present disclosure also provides compositions and methods of using these rAAV to treat muscular dystrophy, such as, e.g., Duchenne Muscular Dystrophy. The present disclosure also provides genotyping a subject's DMD gene to determine if rAAV gene therapy should be contraindicated.

This disclosure provides, in particular, oligonucleotide compositions and methods thereof. In some embodiments, the oligonucleotides comprise various chemical modifications of sugars, nucleobases, and / or internucleotide bonds and their patterns, and are available for exon skipping. In some embodiments, this disclosure provides techniques for use with exon 44 of a jumping dystrophin (DMD) transcript. In some embodiments, this disclosure provides techniques for modulating DMD transcript splicing. In some embodiments, this disclosure provides methods for preventing or treating conditions, disorders, or diseases including Duchenne muscular dystrophy.

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 internucleotidic 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.

This disclosure provides, in particular, oligonucleotide compositions and methods thereof. In some embodiments, the oligonucleotides comprise various chemical modifications of sugars, nucleobases, and / or internucleotide bonds and their patterns, and are usable for exon skipping. In some embodiments, this disclosure provides techniques for use in exon 52 of jumping dystrophin (DMD) transcripts. In some embodiments, this disclosure provides techniques for modulating DMD transcript splicing. In some embodiments, this disclosure provides methods for preventing or treating conditions, disorders, or diseases including Duchenne muscular dystrophy.

The invention, in general, relates to the field of Adeno-associated virus (AAV). More particularly, the present invention relates to bioengineered AAV9 vector carrying optimised transgene for Duchenne muscular dystrophy gene therapy. The present invention particularly provides an engineered AAV9 vector containing a microdystrophin therapeutic gene optimized for codon usage, under the control of a ubiquitous promoter and a Kozak sequence, aimed at gene therapy for Duchenne muscular dystrophy. The improved AAV9 vector amplifies the therapeutic efficacy of DMD gene therapy.

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.

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 internucleotidic linkages and patterns thereof and are useful for exon skipping. In some embodiments, the present disclosure provides technologies useful for skipping exon 51 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 systems, compositions, and methods for modifying the human dystrophin gene (DMD). Systems, compositions, and methods may comprise a compact Type V CRISPR-associated (Cas) protein, an RNA-dependent DNA polymerase, and / or one or more guide nucleic acids or uses thereof. These systems, compositions, and methods may be useful for treating diseases such as Duchenne muscular dystrophy (DMD).

The present disclosure relates to compositions and methods for treating muscular dystrophy.