rAAV compositions for gene therapy

Abstract

The subject invention concerns materials and methods for gene therapy. One aspect of the invention pertains to vectors which can be used to effect genetic therapy in animals or humans having genetic disorders where expression of high levels of a protein of interest are required to treat or correct the disorder. The subject invention also pertains to methods for treating animals or humans in need of gene therapy to treat or correct a genetic disorder. The materials and methods of the invention can be used to provide therapeutically effective levels of a protein that is non-functional, or that is absent or deficient in the animal or human to be treated. In one embodiment, the materials and methods can be used to treat alpha-1-antitrypsin deficiency.

41 . A recombinant adeno-associated viral vector comprising a polynucleotide that encodes an α-1-antitrypsin polypeptide.  
     
     
         42 . The vector of  claim 41 , wherein said vector comprises a promoter operably linked to said polynucleotide.  
     
     
         43 . The vector of  claim 42 , wherein said promoter is selected from the group consisting of a CMV promoter, a hybrid CMV enhancer/β-actin promoter, an EF1 promoter, an U1a promoter and an U1b promoter.  
     
     
         44 . The vector of  claim 42 , wherein said promoter is an inducible promoter selected from the group consisting of a Tet-inducible promoter and a VP16-LexA promoter.  
     
     
         45 . The vector of  claim 42 , wherein said vector further comprises an enhancer.  
     
     
         46 . The vector of  claim 45 , wherein said vector further comprises a CMV enhancer.  
     
     
         47 . The vector of  claim 45 , wherein said enhancer comprises a synthetic enhancer.  
     
     
         48 . The vector of  claim 47 , wherein said synthetic enhancer comprises a muscle-specific enhancer.  
     
     
         49 . The vector of  claim 41 , wherein said vector comprises at least a first intron sequence.  
     
     
         50 . The vector of  claim 49 , wherein said intron sequence comprises intron II from a mammalian gene encoding α-1-antitrypsin.  
     
     
         51 . The vector of  claim 41 , wherein said polynucleotide encodes a human α-1-antitrypsin polypeptide.  
     
     
         52 . The vector of  claim 41 , wherein said vector is selected from the group consisting of DE-AT (SEQ ID NO:3)) E-AT (SEQ ID NO:2), C-AT (SEQ ID NO:1), C-AT2(SEQ ID NO:7), p43C-AT (SEQ ID NO:4), p43CB-AT (SEQ ID NO:6), p43C-AT-IN (SEQ ID