Viral vectors and host cells and methods of making and using them

Abstract

The present invention provides a conditionally replicating viral vector, methods of making, modifying, propagating, selectively packaging, and using such a vector, isolated molecules of specified nucleotide and amino acid sequences relevant to such vectors, a pharmaceutical composition and a host cell comprising such a vector, and methods of using such a vector and a host cell.

1 . A conditionally replicating human immunodeficiency viral (HIV) vector comprising:
 (a) a nucleic acid comprising a human immunodeficiency virus 1 (HIV-1) genome sequence;   (b) an HIV-1 5′ long terminal repeat (LTR) and an HIV-1 3′ LTR;   (c) a heterologous nucleic acid operably linked to the 5′ LTR, wherein the heterologous nucleic acid comprises an antisense sequence complementary to a wild-type HIV-1 sequence necessary for packaging into progeny virions, thereby providing the vector with a selective advantage for packaging over the wild-type HIV-1 sequence;   (d) a lentiviral rev responsive element (rre) sequence; and   (e) a “ψ” or “psi” packaging signal;   wherein the conditionally replicating HIV vector lacks all full-length protein-encoding sequences encoding any HIV functional protein, and the antisense sequence inhibits encapsidation of a replication-competent HIV genome.   
     
     
         2 . The conditionally replicating HIV vector of  claim 1 , wherein the vector further comprises a sequence required for RNA transcription, tRNA primer binding, dimerization and/or packaging. 
     
     
         3 . The conditionally replicating vector of  claim 1 , wherein the vector is formulated with a pharmaceutically acceptable carrier. 
     
     
         4 . A recombinant host cell comprising the conditionally replicating HIV vector of  claim 1 . 
     
     
         5 . The recombinant host cell of  claim 4 , wherein the recombinant host cell provides at least one of the nucleotide sequences encoding a functional Tat, Env, Nef, Gag, and/or another functional HIV protein.