Capsid-modified recombinant adenovirus and methods of use

Abstract

The present invention describes a recombinant adenoviral vector in which a single-chain antibody has been introduced into the minor capsid proteins, pIIIa or pIX, so that the adenoviral vector can be targeted to a particular cell type. Additionally disclosed is a method of using the recombinant adenoviral vector in targeted gene therapy.

What is claimed is:  
     
         1 . A recombinant adenovirus, wherein said adenovirus comprises a modified gene encoding a modified adenoviral capsid protein.  
     
     
         2 . The recombinant adenovirus of  claim 1 , wherein said gene encoding said capsid protein is modified by introducing a single chain antibody into said gene.  
     
     
         3 . The recombinant adenovirus of  claim 2 , wherein said single chain antibody is directed towards a protein, wherein said protein is specific to a cell type.  
     
     
         4 . The recombinant adenovirus of  claim 3 , wherein said cell type is a tumor cell.  
     
     
         5 . The recombinant adenovirus of  claim 3 , wherein said protein is a cell-surface protein.  
     
     
         6 . The recombinant adenovirus of  claim 1 , wherein said capsid gene is a minor capsid gene.  
     
     
         7 . The recombinant adenovirus of  claim 6 , wherein said minor capsid gene is selected from the group consisting of pIIIa and pIX.  
     
     
         8 . The recombinant adenovirus of  claim 1 , wherein said modified capsid protein retains its native display profile.  
     
     
         9 . The recombinant adenovirus of  claim 1 , wherein said adenovirus exhibits CAR-independent gene transfer.  
     
     
         10 . The recombinant adenovirus of  claim 1 , wherein said adenovirus further comprises an additional modification to an adenovirus fiber knob, wherein said modification to said fiber knob ablates the native tropism of said adenovirus.  
     
     
         11 . The recombinant adenovirus of  claim 1 , wherein the adenoviral vector encoding said adenovirus further comprises a therapeutic gene.  
     
     
         12 . A method of providing gene therapy to an individual in need of such treatment, comprising the steps of: 
 administering to said individual an effective amount of the recombinant adenovirus of  claim 11 .    
     
     
         13 . The method of  claim 12 , wherein said administration is systemically.  
     
     
         14 . The recombinant adenovirus of  claim 11 , wherein said therapeutic gene is the herpes simplex virus-thymidine kinase gene.  
     
     
         15 . A method of killing tumor cells in an individual in need of such treatment, comprising the steps of: 
 administering to said individual an effective amount of the recombinant adenovirus of  claim 14;  and    treating said individual with ganciclovir.    
     
     
         16 . The method of  claim 15 , wherein said administration is systemically.  
     
     
         17 . A method of increasing the ability of an adenovirus to transduce a specific cell type, comprising the step of: 
 modifying a gene encoding an adenoviral capsid protein, wherein said modification increases the ability of said adenovirus to transduce a specific cell type.    
     
     
         18 . The method of  claim 17 , wherein said gene encoding said capsid protein is modified by introducing a single chain antibody into said gene.  
     
     
         19 . The method of  claim 18 , wherein said single chain antibody is directed towards a protein, wherein said protein is specific to a cell type.  
     
     
         20 . The method of  claim 19 , wherein said cell type is a tumor cell.  
     
     
         21 . The method of  claim 19 , wherein said protein is a cell-surface protein.  
     
     
         22 . The method of  claim 17 , wherein said capsid gene is a minor capsid gene.  
     
     
         23 . The method of  claim 22 , wherein said minor capsid gene is selected from the group consisting of pIIIa and pIX.  
     
     
         24 . The method of  claim 17 , wherein said modified capsid protein retains its native display profile.  
     
     
         25 . The method of  claim 17 , wherein said adenovirus exhibits CAR-independent gene transfer.  
     
     
         26 . The method of  claim 17 , wherein said adenovirus further comprises an additional modification to an adenovirus fiber knob, wherein said modification to said fiber knob ablates the native tropism of said adenovirus.  
     
     
         27 . The method of  claim 17 , wherein the adenoviral vector encoding said adenovirus further comprises a therapeutic gene.