112 results about "Dystrophin" 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.

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

The present disclosure provides gene constructs that encode a truncated dystrophin protein. The present disclosure also provides systems and methods for delivering a truncated dystrophin protein in a subject, and methods for treating a subject having a dystrophin-associated disease or disorder, e.g., muscular dystrophy, e.g., 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.

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.

The present invention concerns a quasidystrophin (QD) having the structure CH1CH2H1R1R2R3H2R8R9 in its N-terminal part and advantageously further comprising the R16 and R17 rod domains, as well as the dual AAV vector system which allows producing it.

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.

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

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.

Provided is an invention based, in part, on novel gene constructs that encode a microdystrophin protein for use in gene therapy. The microdystrophin gene constructs and expression cassettes were engineered for improved therapy with respect to efficacy, potency and safety to the subject when expressed by a viral vector in muscle cells and / or CNS cells.

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.

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.

Synthetic nucleic acids encoding mini and microdystrophin genes comprising the membrane binding motifs or domains of the R10-R11-R12 region are provided. Also provided are vectors, host cells, and related methods of using the same to treat a subject suffering from Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD) or X-linked dilated cardiomyopathy (XLDC), or for ameliorating one or more adverse effects of DMD, BMD, or XLDC. Also provided are a fusion protein comprising a nNOS binding domain of dystrophin R16-R17 that is operably linked to a syntrophin PDZ domain and synthetic nucleic acids comprising the same that can be used to treat subjects with diseases characterized by loss of sarcolemmal neuronal nitric oxide synthase (nNOS) activity.

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.

An optimized AAV vector for gene therapy of muscular dystrophy is provided. The optimized AAV vector includes a plurality of mutant AAV9 vectors and a microdystrophin transgene (p.AAV-CBA-kozak-μDys). The optimized AAV vector demonstrate increased transduction efficiency, gene expression levels, and can potentially achieve optimal therapeutic efficacy in humans at lower vector doses. The optimized AAV vector also demonstrate improved transduction and dystrophin gene expression in a mice model of Duchenne muscular dystrophy.

The invention relates to the technical field of biomedicine, in particular to a serum protein marker for ossification of ligamentum flavum and application of the serum protein marker. The serum protein marker comprises erythrocyte glucose phosphate isomerase and / or dystrophin associated glycoprotein 1. According to the method, a data-independent quantitative proteomics strategy is utilized to compare a normal healthy control (a patient who does not suffer from ligamentum flavum ossification and needs spinal surgery to take ligamentum flavum tissues) with a ligamentum flavum ossification patient; it is found that ligamentum flavum ossification-related proteins, namely erythrocyte glucose phosphate isomerase (GPI) and dystrophy protein-related glycoprotein 1 (DAG1), with the obviously-changed expression quantity in tissue are beneficial to diagnosis of patients with ligamentum flavum ossification and provide effective targets for development of treatment methods of the ligamentum flavum ossification.

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.

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.

Provided herein are antisense oligonucleotides (AONs), and pharma- ceutically acceptable derivatives thereof, that induce skipping of exon 51 of human dystrophin pre-mRNA. Pharmaceutical compositions containing the AONs, and methods of using the AONs and compositions to treat subjects with Duchenne muscular dystrophy, are also provided.

The invention features methods of treating a subject having Duchenne muscular dystrophy by administering an activin A and myostatin signaling inhibitor in combination with a dystrophin exon skipping therapy. The activin A and myostatin signaling inhibitor may be an activin A antibody or an antigen binding fragment thereof and an anti-myostatin protein (e.g., a myostatin antibody or an antigen binding fragment thereof or an anti-myostatin adnectin recombinant protein), an ActRII antibody or an antigen binding fragment thereof, or an extracellular ActRII ligand trap.

Disclosed herein are adapted dystrophin proteins (e.g., adapted mini- or micro-dystrophin proteins), nucleic acid molecules and vectors encoding the same, as well as methods of treating a muscular dystrophy (e.g., Duchenne or Becker muscular dystrophy), for example by gene therapy comprising the adapted dystrophin proteins, the nucleic acid molecules, or the vectors of the disclosure.

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).