Use of rapamycin to inhibit immune response and induce tolerance to gene therapy vector and encoded transgene products

Abstract

Disclosed are methods for transient co-administration of rapamycin together with a gene therapy vector encoding a transgene. The present invention is directed to inhibiting the immune response of a host to the administered gene therapy vector and encoded transgene product, thus allowing persistent transgene expression and repeated administration of the gene therapy product to the host. The present invention is also of relevance in genetic disease patients that mount immune responses to protein replacement therapies in which case the present invention provides for transient co-administration of rapamycin together with protein replacement therapy. In a further aspect of the invention, co-administration of rapamycin could inhibit a secondary immune response in a host that has been pre-immunized with the gene therapy vector or pre-immunized with the protein product encoded by the transgene.

We claim:  
     
         1 . A method for inhibiting the immune response of a host to a gene therapy vector and encoded trangene product, said method comprising 
 co-administering the gene therapy vector with an effective amount of rapamycin.    
     
     
         2 . The method of  claim 1 , wherein the gene therapy vector is an adenoviral vector containing a deletion of adenoviral gene sequences.  
     
     
         3 . The method of  claim 1 , wherein the transgene encodes a protein selected from the group consisting of glucocerebrosidase, alpha-galactosidase A, beta-galactosidase, sphingomyelinase, iduronate sulfatase, alpha-glucosidase and alpha-iduronidase.  
     
     
         4 . The method of  claim 1 , wherein the trangene encodes a protein selected from the group consisting of Factor VIIA, Factor VIII or Factor IX.  
     
     
         5 . A method for allowing persistent expression of a transgene, said method comprising co-administering the gene therapy vector with an effective amount of rapamycin.  
     
     
         6 . The method of  claim 5 , wherein the gene therapy vector is an adenoviral vector containing a deletion of adenoviral gene sequences.  
     
     
         7 . The method of  claim 5 , wherein the transgene encodes a protein selected from the group consisting of glucocerebrosidase, alpha-galactosidase A, beta-galactosidase, sphingomyelinase, iduronate sulfatase, alpha-glucosidase and alpha-iduronidase.  
     
     
         8 . The method of  claim 5 , wherein the trangene encodes a protein selected from the group consisting of Factor VIIA, Factor VIII or Factor IX.