Defective sindbis viral vectors

Abstract

Disclosed herein are new defective Sindbis viral vectors made from wild type Ar-339 Sindbis virus, with differences in replicase and envelope proteins between JT vectors and consensus Sindbis virus sequences, and also between JT and Ar-339 vectors. Also disclosed are plasmids used for the production of the vectors, methods for producing the vectors, methods for treating mammals suffering from tumors and pharmaceutical formulations for use in the treatment methods.

1 - 10 . (canceled) 
     
     
         11 . A defective Sindbis viral vector produced by the method comprising the steps of:
 (a) providing a linearized replicon plasmid comprising the nucleotide sequence consisting of the sequence as set forth in SEQ ID NO: 36 and a linearized Helper plasmid comprising the nucleotide sequence consisting of the sequence as set forth in SEQ ID NO: 39;   (b) transcribing said replicon plasmid and said Helper plasmid to produce RNA;   (c) collecting the RNA transcribed in step (b) and transfecting cells with said RNA;   (d) incubating said transfected cells in step (c) for a time and at a temperature effective for producing defective Sindbis viral vectors; and   (e) collecting said defective Sindbis viral vectors from the medium of said transfected cells.   
     
     
         12 . The defective Sindbis viral vector of  claim 11  wherein said vector is Mut-4. 
     
     
         13 . The defective Sindbis viral vector of  claim 11  wherein said cells are selected from BHK-21, ES-2, ES-2/Fluc and MOSEC cells. 
     
     
         14 . A method for treating a mammal suffering from a tumor comprising administering to a mammal in need of such treatment a therapeutically effective amount of a Mut-4 defective Sindbis viral vector. 
     
     
         15 . A pharmaceutical formulation for treating a mammal suffering from a tumor comprising a Mut-4 defective Sindbis viral vector and a pharmaceutically acceptable carrier or diluent.