HIV-Derived Lentiviral Vectors: Current Progress toward Gene Therapy and DNA Vaccination

Lentiviral vectors are promising gene delivery tools capable of transducing a variety of dividing and non-dividing cells, including pluripotent stem cells which are refractory for transduction by murine retroviruses. Although there is a growing debate on the safety of lentiviral vectors for gene transfer, in particular for those derived from human immunodeficiency viruses, type one (HIV-1) and type two (HIV-2), these vectors are envisioned to possess several advantages. Importantly, they can be utilized not only for transducing specific target cells or for in vivo gene therapy of HIV infection and acquired immunodeficiency syndrome (AIDS), but also in a pseudotype recombinant form can be used for different target cells including neurological and cancer cells. For HIV-2, the most com- pelling advantages are: (i) its reduced ability to recombine with resident HIV-1 genome; (ii) its ability to induce in recipients antibodies which can be distinguished from host immune response to HIV-1; (iii) HIV-2 is apparently less pathogenic; and (iv) may downregulate HIV-1 expression. This review will summarize new developments on HIV-1 vectors, while focusing on alternate strategies toward developing HIV-2-based vectors.