Development of a self-inactivating, minimal lentivirus vector based on simian immunodeficiency virus

In contrast to oncoviruses, lentiviruses do not require target cell divisio n for integration into the host genome. Lentiviral vectors can therefore ex pand the spectrum of target cells susceptible to retroviral gene transfer. To analyze whether vectors based on simian immunodeficiency viruses (SIVs) could be used for gene transfer, a three-plasmid vector-packaging system wa s developed, in which Gag-Pol and the vector itself are of SIV origin, whil e Env is derived either from SIV, amphotropic murine leukemia virus (MuLV), or the G glycoprotein of vesicular stomatitis virus (VSV-G), To increase t he safety of the SIV vector system, a self-inactivating SIV vector was cons tructed. After optimization of the SIV gag-pol expression plasmid, a minima l SIV vector, which contained only SIV sequences present on the multiply sp liced nef transcript, could still be produced at titers of 2 x 10(5) infect ious units/ml. Growth-arrested cells could be transduced with this vector e ven if vif, vpr, vpx, and nef had been deleted from the packaging construct and the vector.