Adeno-associated virus vector delivery of muscle specific micro-dystrophin to treat muscular dystrophy
AssigneeResearch Institute At Nationwide Children's Hospital
InventorsLouise Rodino-Klapac, Jerry R. Mendell
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Abstract
The invention provides gene therapy vectors, such as adeno-associated virus (AAV) vectors, expressing a miniaturized human micro-dystrophin gene and method of using these vectors to express micro-dystrophin in skeletal muscles including diaphragm and cardiac muscle and to protect muscle fibers from injury, increase muscle strength and reduce and/or prevent fibrosis in subjects suffering from muscular dystrophy.
Claims21
A composition comprising a polynucleotide comprising the nucleotide sequence of SEQ ID NO:
- 9.
-10. (canceled)
A method of expressing a microdystrophin gene in a cell comprising contacting the cell with a recombinant adeno-virus associated (rAAV) serotype rh.74 comprising a polynucleotide comprising the nucleotide sequence of SEQ ID NO:
- 1 operably linked to an MHCK7 promoter.
A method of decreasing serum CK levels in a subject in need thereof, the method comprising administering to the subject a recombinant adeno-virus associated (rAAV) serotype rh.74 comprising a polynucleotide comprising the nucleotide sequence of SEQ ID NO:
- 1 operably linked to an MHCK7 promoter.
A method of increasing microdystrophin positive fibers in muscle tissue of a subject comprising administering to the subject a recombinant adeno-virus associated (rAAV) serotype rh.74 comprising a polynucleotide comprising the nucleotide sequence of SEQ ID NO:
- 1 operably linked to an MHCK7 promoter.
A method of treating Duchenne muscular dystrophy in a human subject in need thereof comprising administering an recombinant adeno-virus associated (rAAV) serotype rh.74 comprising a polynucleotide comprising the nucleotide sequence of SEQ ID NO:
- 1 operably linked to a promoter sequence of SEQ ID NO:
- 7, wherein the rAAV is administered intravenously at a dose of 2×1014 vg/kg, and wherein the human subject has a AAVrh.74 antibody titer<1:400 as determined by ELISA immunoassay before administration of the rAAV serotype rh.74 to the subject.
Dependencies are inferred from the claim text.