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.

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 said virus is selected from Alphavirus, Adenovirus, Adeno Associated Virus and Herpesvirus.  
     
     
         3 . The virus envelope protein of  claim 2 , wherein the virus is an Alphavirus.  
     
     
         4 . The virus envelope protein of  claim 3 , wherein the Alphavirus is a Sindbis virus and the envelope protein is an E2 protein.  
     
     
         5 . The virus envelope protein of  claim 2 , wherein the IgG binding domain of Protein A is a ZZ domain.  
     
     
         6 . The virus envelope protein of  claim 5 , wherein said 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 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 from a virus selected from Adenovirus, Adeno associated virus and Herpesvirus and wherein said chimeric envelope protein alters the binding of said virus to its natural receptor, and an antibody directed against a surface protein on said target cell.    
     
     
         11 . The complex of  claim 10  wherein the IgG binding domain of Protein A is a ZZ domain.  
     
     
         12 . A viral vector comprising an envelope protein from a virus selected from Adenovirus, Adeno Associated Virus and Herpesvirus, wherein said envelope protein is modified by the insertion of an IgG binding domain of Protein A.  
     
     
         13 . A viral vector comprising an Alphavirus envelope protein modified by insertion of an IgG binding domain of protein A.  
     
     
         14 . The viral vector of  claim 13  wherein the Alphavirus is a Sindbis virus and the envelope protein is an E2 protein.  
     
     
         15 . The viral vector of  claim 14 , wherein the IgG binding domain of Protein A is inserted between the amino acid residues 71 and 74 of said E2 protein.  
     
     
         16 . The viral vector of  claim 15  wherein the IgG binding domain of Protein A is a ZZ domain.  
     
     
         17 . An isolated nucleic acid encoding a virus envelope protein modified by insertion of an IgG binding domain of Protein A.  
     
     
         18 . The nucleic acid of  claim 17 , wherein the virus is an Alphavirus and the envelope protein is an E2 protein.  
     
     
         19 . The nucleic acid of  claim 17  wherein the IgG binding domain of Protein A is a ZZ domain.  
     
     
         20 . The nucleic acid of  claim 19 , wherein the IgG binding domain of protein A is inserted between amino acid residues 71 and 74 of said E2 protein.  
     
     
         21 . The nucleic acid of  claim 17 , wherein the virus is selected from Adenovirus, Adeno Associated Virus and Herpesvirus.  
     
     
         22 . An isolated nucleic acid encoding an envelope protein modified by insertion of an IgG binding domain of Protein A, wherein said envelope protein is from a virus selected from Adenovirus, Adeno Associated Virus and Herpesvirus.