Recombinant Adeno-Associated Virus Delivery of Alpha-Sarcoglycan Polynucleotides

Abstract

The present invention relates to recombinant adeno-associated virus (rAAV) delivery of an alpha-sarcoglycan gene. The invention provides rAAV products and methods of using the rAAV in the treatment of limb girdle muscular dystrophies such as LGMD2D.

1 .- 23 . (canceled) 
     
     
         24 . A recombinant AAV vector comprising a polynucleotide encoding alpha-sarcoglycan, wherein the polynucleotide comprises a nucleotide sequence at least 95% identical to SEQ ID NO: 3. 
     
     
         25 . The recombinant AAV vector of  claim 24 , wherein the polynucleotide sequence encoding alpha-sarcoglycan comprises the nucleotide sequence set forth in SEQ ID NO: 3. 
     
     
         26 . The recombinant AAV vector of  claim 24 , wherein the vector is of the serotype AAV-1, AAV-2, AAV-3, AAV-4, AAV-5, AAV-6, AAV-7, AAV-8, AAV-9, AAV-10, AAV-11 or AAV rh.74. 
     
     
         27 . The recombinant AAV vector of  claim 26 , wherein the vector is of the serotype AAV rh.74. 
     
     
         28 . The recombinant AAV vector of  claim 24 , wherein the polynucleotide sequence is operably linked to a muscle-specific control element. 
     
     
         29 . The recombinant AAV vector of  claim 28 , wherein the muscle-specific control element is human skeletal actin gene element, cardiac actin gene element, myocyte-specific enhancer binding factor (MEF) element, muscle creatine kinase (MCK) promoter, truncated MCK (tMCK) promoter, myosin heavy chain (MHC) control element, MHCK7 promoter, C5-12, murine creatine kinase enhancer element, skeletal fast-twitch troponin c gene element, slow-twitch cardiac troponin c gene element, slow-twitch troponin gene element, hypoxia response element (HRE), steroid-inducible element or glucocorticoid response element (GRE). 
     
     
         30 . The recombinant AAV vector of  claim 29 , wherein the muscle-specific control element is the truncated MCK (tMCK) promoter. 
     
     
         31 . The recombinant AAV vector of  claim 24 , wherein the vector comprises a AAV rh.74 capsid that comprises a sequence that is at least 95% identical to SEQ ID NO: 2. 
     
     
         32 . The recombinant AAV vector of  claim 24 , wherein the AAV rh.74 capsid comprises the sequence of SEQ ID NO: 2. 
     
     
         33 . A composition comprising the recombinant AAV vector of  claim 24  and a pharmaceutically acceptable carrier, diluent or adjuvant. 
     
     
         34 . A method of improving muscle function in a patient afflicted with limb girdle muscular dystrophy type 2D (LGMD 2D) comprising administering to the patient, a therapeutically effective amount of the recombinant AAV vector of  claim 24 . 
     
     
         35 . A method of treating muscular dystrophy in a patient in need thereof comprising administering to the patient, a therapeutically effective amount of the recombinant AAV vector of  claim 24 . 
     
     
         36 . The method of  claim 35 , wherein the muscular dystrophy is limb girdle muscular dystrophy type 2D (LGMD 2D).