Helper virus-free transfer of human immunodeficiency virus type 1 vectors

University of Cambridge Department of Medicine, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK Recombinant vectors based on the type 1 human immunodeficiency virus (HIV-1) can be used to deliver genes into cells expressing the HIV receptor, CD4. We have used a transient RNA packaging system to compare the safety and efficacy of HIV-1 vector transduction by wild-type and replication-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 events were required to form an infectious genome. Other forms of attenuation, such as deletion of the 5' region, were inadequate to prevent helper virus transmission. Vector transduction by the wild-type and non-replicating helper viruses occurred with comparable efficiency except in instances where efficient vector RNA expression was dependent upon transactivating factors supplied by the helper virus. These data demonstrate the feasibility of safe gene transfer using HIV-1 vectors. * Author for correspondence. Fax +44 1223 336846. Present address: Division of Human Retrovirology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA. Received 11 July 1994; accepted 24 October 1994.