HSV viral vector

Abstract

The present invention relates to a recombinant herpes simplex virus (HSV) viral vector genome which has substantially lost its transducing properties as a result of a DNA sequence change in the gene coding for Vmw65 protein and also comprises an expressable heterologous gene inserted into a region of the HSV genome which is non-essential for the culture of the virus, the gene being under the control of the immediate early (IE1) gene enhancer of cytomegalovirus (CMV) and to the use of the recombinant HSV genome in therapy and vaccination.

That which is claimed:  
     
         1 . A recombinant herpes simplex virus (HSV) viral vector genome which comprises: 
 (i) a DNA sequence change in the gene coding for Vmw65 protein such as to substantially remove transinducing properties thereof; and    (ii) an expressable heterologous gene inserted into a region of the HSV genome which is non-essential for culture of the virus, the gene being under the control of the immediate early 1 (IE1) gene enhancer of cytomegalovirus (CMV).    
     
     
         2 . A recombinant HSV genome according to  claim 1 , wherein the CMV gene enhancer is the human enhancer.  
     
     
         3 . A recombinant HSV genome according to  claim 2 , wherein the CMV gene enhancer contains sequence variations such that the enhancer properties are not affected.  
     
     
         4 . A recombinant HSV genome according to  claim 1 , wherein said herpes simplex virus is HSV-1.  
     
     
         5 . A recombinant HSV genome according to  claim 1 , wherein the sequence change in the gene coding for Vmw65 is an insertion.  
     
     
         6 . A recombinant HSV genome according to  claim 5 , wherein the insertion is of 3-72 base pairs.  
     
     
         7 . A recombinant HSV genome according to  claim 1 , wherein the sequence change in the gene coding for Vmw65 protein is between amino acids 289 and 480 of the protein.  
     
     
         8 . A recombinant HSV genome according to  claim 1 , wherein said expressable heterologous gene is selected from the group consisting of: 
 (a) human, rat, or mouse tyrosine hydroxylase genes 1, 2 or 3;    (b) human, rat, or mouse nerve growth factor;    (c) human, rat or mouse hypoxanthine-guanine phosphoribosyl transferase gene;    (d) human beta-hexosaminidase alpha chain gene; and    (e) human immunodeficiency virus (HIV) nef gene.    
     
     
         9 . A recombinant HSV genome according to  claim 1 , wherein the heterologous gene is inserted in the coding sequence or in a flanking control region of at least one HSV-1 gene selected from the group consisting of the UL23 gene, the RL1 gene, the RL2 gene, the locus encoding the latency associated transcripts, the UL2 gene, the UL3 gene, the UL4 gene, the UL10 gene, the UL11 gene, the UL13 gene, the UL16 gene, the UL20 gene, the UL24 gene, the UL40 gene, the UL41 gene, the UL43 gene, the UL44 gene, the UL45 gene, the UL46 gene, the UL47 gene, the UL50 gene, the UL55 gene, the UL56 gene, the US1 gene, the US2 gene, the US3 gene, the US4 gene, the US5 gene, the US7 gene, the US8 gene, the US9 gene, the US10 gene, the US11 gene, and the US12 gene.  
     
     
         10 . An HSV mutant containing the genome of  claim 1 .  
     
     
         11 . A method of treating disease comprising administering the recombinant HSV genome of  claim 1  to a subject in need of such treatment.  
     
     
         12 . A method of vaccination comprising administering the recombinant HSV genome of  claim 1  to a subject in need of vaccination.  
     
     
         13 . A pharmaceutical composition comprising the recombinant HSV genome of  claim 1  in admixture with a pharmaceutically acceptable carrier.