MINIMAL LENTIVIRAL VECTOR SYSTEM

摘要

A lentiviral vector system is described. The system comprises a lentiviral transfer vector and a packaging construct. The transfer vector comprises (a) a 5' LTR; (b) a 3' LTR comprising a polyadenylation signal; (c) a minimal packaging signal, (d) (i) at least one heterologous upstream enhancer (UE) sequences, and/or (ii) at least one additional copy of endogenous UE sequences operatively associated with said polyadenylation signal; and (e) a PRE. The packaging construct comprises a nucleic acid encoding and expressing a lentiviral Gag nucleic acid (preferably Gag and Pol). Preferably the lentiviral Gag nucleic acid is a mutated Gag nucleic acid containing one or more substitution mutations, wherein said mutated Gag nucleic acid encodes the same amino acid sequence as the corresponding unmutated Gag nucleic acid, but differs from the nucleic acid sequence of said corresponding unmutated Gag nucleic acid sequence due to the degeneracy of the genetic code. Preferably the packaging construct further comprises a heterologuous nucleic acid encoding and expressing an adenovirus VA RNA. The transfer vector and packaging construct can be used together in a producer cell to produce viral particles.