Compositions and methods for treating lysosomal storage disease

Abstract

The present invention provides recombinant viral and non-viral vectors comprising a transgene encoding a biologically active human lysosomal enzyme that are able to infect and/or transfect and sustain expression of the biologically active human lysosomal enzyme transgene in mammalian cells deficient therein. In addition, methods are provided for providing a biologically active human lysosomal enzyme to cells deficient therein, which comprises introducing into the cells a vector comprising and expressing a transgene encoding the biologically active human lysosomal enzyme, wherein the vector is taken up by the cells, the transgene is expressed and biologically active enzyme is produced. The cells may be infected and/or transfected by the vector, dependent upon whether the vector is a viral vector and/or plasmid or the like. The invention also provides a method of supplying a biologically active human lysosomal enzyme to other distant cells deficient therein wherein the transfected and/or infected cells harboring the vector secrete the biologically active enzyme which is then taken up by the other deficient cells. In a preferred embodiment the present invention provides for sustained production of biologically human active α-galactosidase A in cells of Fabry individuals that are deficient in said enzyme.

1 . A method for providing biologically active acid β-glucosidase to cells deficient therein, said method comprising administration of a vector to cells in vivo comprising and expressing a transgene encoding said biologically active acid β-glucosidase, wherein the vector is taken up by the cells, the transgene is expressed therein and said biologically active acid β-glucosidase is produced. 
   
   
       2 . A method according to  claim 1 , wherein the cells harboring the vector secrete the biologically active enzyme which is taken up by other cells deficient in the enzyme. 
   
   
       3 . A method according to  claim 1 , wherein the vector is a viral vector. 
   
   
       4 . A method according to  claim 3 , wherein the viral vector is adenovirus. 
   
   
       5 . A method according to  claim 4 , wherein the adenovirus is complexed with DEAE-dextran. 
   
   
       6 . A method according to  claim 2 , wherein the vector is a viral vector. 
   
   
       7 . A method according to  claim 6 , wherein the viral vector is adenovirus. 
   
   
       8 . A method according to  claim 7 , wherein the adenovirus is complexed with DEAE-dextran. 
   
   
       9 . A method according to  claim 1 , wherein the vector is plasmid. 
   
   
       10 . A method according to  claim 9 , wherein the plasmid is complexed with a cationic lipid. 
   
   
       11 . A method according to  claim 2 , wherein the vector is plasmid. 
   
   
       12 . A method according to  claim 11 , wherein the plasmid is complexed with a cationic lipid. 
   
   
       13 . A composition comprising the plasmid vector of  claim 9  complexed with a cationic lipid. 
   
   
       14 . A composition according to  claim 13 , wherein the cationic lipid is N 4 -spermine cholesteryl carbamate. 
   
   
       15 . A composition comprising the plasmid vector of  claim 11  complexed with a cationic lipid. 
   
   
       16 . A composition according to  claim 11 , wherein the cationic lipid is N 4 -spermine cholesteryl carbamate.