Viral vectors having chimeric envelope proteins containing the IgG-binding domain of protein A

Abstract

The invention involves viral vectors that can be used to tranduce a target cell, i.e. to introduce genetic material into the cell. The targets of interest are eukaryotic cells and particularly human cells. The transduction can be done in vivo or in vitro. More particularly the invention concerns viral vectors that have chimeric envelope proteins and contain the IgG-binding domain of protein A. These vectors when used in conjunction with antibodies targeting a particular cell are particularly useful for gene therapy.

What is claimed is:  
     
         1 . A virus envelope protein modified by insertion of an IgG binding domain of Protein A.  
     
     
         2 . The virus envelope protein of  claim 1 , wherein the virus is an Alphavirus.  
     
     
         3 . The virus envelope protein of  claim 2 , wherein the Alphavirus is a Sindbis virus and the envelope protein is an E2 protein.  
     
     
         4 . The virus envelope protein of  claim 1 , wherein the Fc binding domain of protein A is a ZZ domain.  
     
     
         5 . The Sindbis virus E2 protein of  claim 3 , wherein the Fc binding domain of protein A is a ZZ domain.  
     
     
         6 . The Sindbis virus E2 protein of  claim 3 , wherein the Fc binding domain of protein A is inserted between amino acid residues  71  and  74  of said E2 protein.  
     
     
         7 . A complex for transducing a target cell comprising 
 a viral vector comprising a chimeric envelope protein containing    an IgG binding domain of Protein A sufficient to bind an Fc domain of an antibody, wherein said envelope protein is a Sindbis E2 protein and wherein said chimeric envelope protein alters the binding of said E2 protein to its natural receptor; and    an antibody directed against a surface protein on said target cell.    
     
     
         8 . The complex of  claim 7 , wherein the IgG binding domain of protein A is a ZZ domain.  
     
     
         9 . The complex of  claim 7  wherein the IgG binding domain of protein A is inserted between amino acid residues  71  and  74  of said E2 protein.  
     
     
         10 . A viral vector comprising an Alphavirus envelope protein modified by insertion of an IgG binding domain of protein A.  
     
     
         11 . The viral vector of  claim 10  wherein the Alphavirus is a Sindbis virus and the envelope protein is an E2 protein.  
     
     
         12 . The viral vector of  claim 10  wherein the IgG binding domain of protein A is a ZZ domain.  
     
     
         13 . The Sindbis virus E2 protein of  claim 11  wherein the IgG binding domain of protein A is a ZZ domain.  
     
     
         14 . The E2 protein of  claim 11  wherein the IgG binding domain of protein A is inserted between the amino acid residues  71  and  74  of said E2 protein.  
     
     
         15 . An isolated nucleic acid encoding a virus envelope protein modified by insertion of an IgG binding domain of protein A.  
     
     
         16 . The nucleic acid of  claim 15  wherein the virus is an Alphavirus and the envelope protein is an E2 protein.  
     
     
         17 . The nucleic acid of  claim 15  wherein the IgG binding domain of protein A is a ZZ domain.  
     
     
         18 . The nucleic acid of  claim 17  wherein the IgG binding domain of protein A is inserted between amino acid residues  71  and  74  of said E2 protein.