Vectors and methods for gene transfer

Abstract

The present invention provides a recombinant adenovirus comprising coat proteins that lack native binding. In particular, the present invention provides a recombinant adenovirus comprising a penton base protein and a fiber protein, wherein the penton base protein and the fiber protein lack native binding. The present invention further provides a recombinant adenovirus comprising (a) a penton base protein that lacks native binding and (b) a nonnative amino acid sequence that binds a cell-surface binding site.

1 . A recombinant adenovirus comprising a penton base protein and a fiber protein, wherein the penton base protein and fiber protein lack native binding.  
     
     
         2 . The recombinant adenovirus of  claim 1 , wherein the penton base protein is unable to bind an α v  integrin receptor.  
     
     
         3 . The recombinant adenovirus of  claim 2 , wherein the penton base protein lacks a native RGD sequence.  
     
     
         4 . The recombinant adenovirus of  claim 2 , wherein the penton base protein comprises a native RGD sequence that is conformationally inaccessible for binding to the α v  integrin receptor.  
     
     
         5 . The recombinant adenovirus of  claim 1 , wherein the fiber protein trimerizes.  
     
     
         6 . The recombinant adenovirus of  claim 1 , wherein the fiber protein lacks the fiber knob.  
     
     
         7 . The recombinant adenovirus of  claim 6 , wherein the fiber protein trimerizes.  
     
     
         8 . A recombinant adenovirus comprising (a) a penton base protein that lacks native binding and (b) a nonnative amino acid sequence that binds a cell-surface binding site.  
     
     
         9 . The recombinant adenovirus of  claim 8 , wherein the penton base protein is unable to bind an α v  integrin receptor.  
     
     
         10 . The recombinant adenovirus of  claim 8 , wherein the penton base protein lacks a native RGD sequence.  
     
     
         11 . The recombinant adenovirus of  claim 8 , wherein the penton base protein comprises a native RGD sequence that is conformationally inaccessible for binding to the α v  integrin receptor.  
     
     
         12 . The recombinant adenovirus of  claim 8 , wherein the adenovirus further comprises a fiber protein lacking native binding.  
     
     
         13 . The recombinant adenovirus of  claim 12 , wherein the fiber protein trimerizes.  
     
     
         14 . The recombinant adenovirus of  claim 12 , wherein the nonnative amino acid sequence is inserted into the fiber protein or in place of at least a portion of the fiber protein.  
     
     
         15 . The recombinant adenovirus of  claim 14 , wherein the nonnative amino acid sequence is inserted into a knob region of the fiber protein or in place of at least a portion of a knob region of the fiber protein.  
     
     
         16 . The recombinant adenovirus of  claim 15 , wherein the fiber protein trimerizes.  
     
     
         17 . The recombinant adenovirus of  claim 15 , wherein the nonnative amino acid sequence is inserted into an exposed loop of the adenovirus fiber knob or in place of at least a portion of an exposed loop of the adenovirus fiber knob.