Vectors with modified protease-dependent tropism

Abstract

The present invention provides cell fusogenic vectors having replicative ability, whose protease-dependent tropism has been modified. M gene-deficient viral vectors encoding modified F proteins, in which the cleavage site of the F protein of paramyxovirus is modified to be cleaved by different proteases, were produced. In cells transfected with these vectors, the genomic RNA present in the vectors is replicated, and cell fusogenic infection spreads to neighboring cells depending on the presence of other proteases; however, no viral particles are released. The vectors of this invention, encoding the F proteins which are cleaved by proteases whose activity is enhanced in cancer, show cancer growth suppressive effect in vivo.

1 . A nucleic acid encoding a recombinant modified paramyxoviral F protein comprising Pro-Leu-Gly, Pro-Gln-Gly, or Val-Gly-Arg at the cleavage site, wherein the modified paramyxoviral F protein shows cell fusogenicity in the presence of a matrix metalloproteinase or a plasminogen activator. 
     
     
         2 . A viral particle comprising the nucleic acid of  claim 1 .