Non-primate lentiviral vectors and packaging systems

Abstract

The invention provides non-primate lentiviral vectors, packaging cells and packaging plasmids based, for example, on feline and ungulate retroviruses. In particular, the packaging plasmids are designed for expression in human cells (which are also used as packaging cells). The vectors of the invention transduce human cells, including difficult to target non-dividing cells of the hematopoietic and nervous system, in vitro and in vivo. The vectors are suitable for general gene transfer to these cells and for gene therapy to treat conditions mediated by these non-dividing cells including cancer and HIV infection.

What is claimed is:  
     
         1 . A lentivirus transfer vector comprising a 5′ LTR and a 3′ LTR, each of which contains a U3 region, wherein a part or all of a regulatory element of the U3 region of the 5′ LTR is replaced by another regulatory element, operable in a mammalian cell, which is not endogenous to said lentivirus.  
     
     
         2 . The transfer vector of  claim 1 , wherein one or more nucleotide bases of the U3 region of the 3′ LTR are deleted.  
     
     
         3 . The transfer vector of  claim 1 , wherein said regulatory element not endogenous to said lentivirus is a cytomegalovirus enhancer, promoter or enhancer/promoter.  
     
     
         4 . The transfer vector of  claim 1 , wherein said regulatory element not endogenous to said lentivirus is a Rous sarcoma virus enhancer, promoter or enhancer/promoter.  
     
     
         5 . The transfer vector of  claim 1 , wherein said transfer vector further comprises a heterologous gene.  
     
     
         6 . The vector of  claim 1 , wherein said lentivirus is human immunodeficiency virus (HIV).  
     
     
         7 . The transfer vector of  claim 2 , wherein said U 3  region deleted is all of said U3 region except for a 5′ terminal dinucleotide and an att sequence.  
     
     
         8 . The transfer vector of  claim 7 , wherein said U 3  region deleted includes a TATA box sequence.  
     
     
         9 . The transfer vector of  claim 6 , wherein said HIV is HIV-1.