Compositions and methods for treating diseases

Abstract

The present invention provides compositions and methods of use pertaining to rAAV-mediated delivery of therapeutically effective molecules for treatment of diseases such as Pompe disease. These compositions in combination with various routes and methods of administration result in targeted expression of therapeutic molecules in specific organs, tissues and cells.

1 .- 20 . (canceled) 
     
     
         21 . A method for treating GAA deficiency or a lysosomal storage disorder, comprising administering to a subject an effective amount of a composition, wherein the composition comprises a recombinant AAV (rAAV) vector selected from an rAAV2/9 vector, an rAAV2/1 vector, and an rAAV2/8 vector, wherein the rAAV vector comprises a heterologous nucleic acid molecule encoding acid α-glucosidase, and wherein the heterologous nucleic acid is operably linked to a desmin (DES) promoter, a cytomegalovirus (CMV) promoter, a synapsin (SYN) promoter, or a muscle creatine kinase (MCK) promoter, and wherein the step of administering comprises intramuscular, intrathoracic, intraspinal, intracisternal, or intrathecal administration. 
     
     
         22 . The method of  claim 21 , wherein the heterologous nucleic acid molecule encodes human acid alpha-glucosidase (hGAA) polypeptide. 
     
     
         23 . The method of  claim 21 , wherein the promoter is a synapsin (SYN) promoter. 
     
     
         24 . The method of  claim 21 , wherein the promoter is a muscle creatine kinase (MCK) promoter. 
     
     
         25 . The method of  claim 21 , wherein the subject has Pompe disease. 
     
     
         26 . The method of  claim 21 , wherein the subject is a human. 
     
     
         27 . The method of  claim 21 , wherein the step of administering comprises an intrathecal or intraspinal injection. 
     
     
         28 . The method of  claim 21 , wherein the step of administering comprises an intracisternal injection. 
     
     
         29 . The method of  claim 21 , wherein the step of administering comprises an intramuscular injection. 
     
     
         30 . The method of  claim 21 , wherein the step of administering comprises an intrathoracic injection. 
     
     
         31 . The method of  claim 21 , wherein the composition further comprises an acetylcholinesterase (AC1) inhibitor. 
     
     
         32 . The method of  claim 21 , wherein the rAAV vector is an rAAV2/1 vector.