HELPER VIRUS-FREE TRANSFER OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VECTORS

Recombinant vectors based on the type 1 human immunodeficiency virus ( HIV-1) can be used to deliver genes into cells expressing the HIV rece ptor, CD4. We have used a transient RNA packaging system to compare th e safety and efficacy of HIV-1 vector transduction by wild-type and re plication-deficient helper viruses. Helper virus-free vector transfer was consistently achieved when the helper virus gag-pol and env genes were expressed from separate plasmids such that two recombination even ts were required to form an infectious genome. Other forms of attenuat ion, such as deletion of the 5' Psi region, were inadequate to prevent helper virus transmission, Vector transduction by the wild-type and n on-replicating helper viruses occurred with comparable efficiency exce pt in instances where efficient vector RNA expression was dependent up on transactivating factors supplied by the helper virus, These data de monstrate the feasibility of safe gene transfer using HIV-1 vectors.