Truncated dysferlin for treatment of dysferlinopathy
AssigneesThe University of North Carolina at Chapel Hill, Texas Tech University System
InventorsMatthew Louis Hirsch, R. Bryan Sutton
Life of this patent
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Abstract
This invention relates to a truncated dysferlin nucleic acid and protein, vectors (e.g., adeno-associated virus vectors) comprising the nucleic acid and methods of using the same for delivery of dysferlin to a cell or a subject and treating dysferlinopathy.
Claims15
A polynucleotide encoding a truncated variant of a wild-type mammalian dysferlin polypeptide, the wild-type mammalian dysferlin polypeptide comprising an amino acid sequence for each of domains C2A, C2B, C2C, FerA, DysF, C2D, C2E, C2F, C2G, and TM, wherein the truncated variant of the wild-type mammalian dysferlin polypeptide comprises, in order, at least 95% of the amino acid sequence of each of domains C2A, C2B, C2C, FerA, DysF, C2G, and TM of the wild-type mammalian dysferlin polypeptide, wherein at least 95% of the amino acid sequence of each of domains C2D, C2E, and C2F of the wild-type mammalian dysferlin polypeptide is deleted, wherein the truncated variant of the wild-type mammalian dysferlin polypeptide exhibits sarcolemma localization and/or maintains muscle membrane integrity, and wherein the polynucleotide is:
- (a) a polynucleotide comprising a sequence at least 95% identical to any one of SEQ ID NOS:
- 2 or 5 or (b) a polynucleotide comprising a sequence encoding a polypeptide identical to any one of SEQ ID NOS:
- 7 or 10.
A truncated variant of a wild-type mammalian dysferlin polypeptide, the wild-type mammalian dysferlin polypeptide comprising an amino acid sequence for each of domains C2A, C2B, C2C, FerA, DysF, C2D, C2E, C2F, C2G, and TM, wherein the truncated variant of the wild-type mammalian dysferlin polypeptide comprises, in order, at least 95% of the amino acid sequence of each of domains C2A, C2B, C2C, FerA, DysF, C2G, and TM of the wild-type mammalian dysferlin polypeptide, wherein at least 95% of the amino acid sequence of each of domains C2D, C2E, and C2F of the wild-type mammalian dysferlin polypeptide is deleted, wherein the truncated variant of the wild-type mammalian dysferlin polypeptide exhibits sarcolemma localization and/or maintains muscle membrane integrity, and wherein the polypeptide is:
- (a) a polypeptide encoded by a polynucleotide comprising a sequence at least 95% identical to any one of SEQ ID NOS:
- 2 or 5;
- or
- (b) a polypeptide comprising a sequence at least 95% identical to any one of SEQ ID NOS:
- 7 or 10.
Dependencies are inferred from the claim text.