Patent ID: 7332322

Claim:
A Venezuelan equine encephalitis virus replicon RNA, wherein said replicon RNA in a 5′ to 3′ order comprises: a 5′ sequence required for nonstructural protein-mediated amplification; a nucleotide sequence encoding nonstructural proteins nsP1, nsP2, nsP3, and nsP4 of the Venezuelan equine encephalitis virus, wherein said nucleotide sequence encodes one or more of a adaptive mutation(s) nsP2Q739L, nsP2P773S or nsP3L121P; one or more promoters each of which is operably linked to one or more heterologous nucleic acid sequence(s) encoding heterologous protein(s) that replaces one or all of the Venezuelan equine encephalitis virus structural protein genes; a 3′ sequence required for nonstructural protein-mediated amplification; and a polyadenylate tract, wherein the third nucleotide in the 5′ UTR of the replicon is a guanine such that the presence of the guanine as the third nucleotide in the 5′UTR of the replicon and the adaptive mutation(s) are effective in reducing the cytopathogenicity of the replicon upon cellular infection.