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The use of human immunodeficiency virus vectors for gene therapy is hampered by concern over their safety. This concern might be ameliorated, in part, if the viral accessory genes and proteins could be eliminated from the vector genomes and particles. Here we describe a minimal vector system that is capable of transducing nondividing cells and which does not contain tat, vif,vpr, vpu, and nef.

The 5′ control region of the yeast phosphoglycerate kinase gene (PGK) was fused to the coding sequence of a human interferon‐alpha. This PGK‐interferon fusion was then introduced into yeast on a high copy number 2mu‐based plasmid vector. Strains containing this plasmid produced a PGK‐interferon‐alpha fusion protein as 1‐2% of cell protein and the expression of interferon activity was regulated by the availability of a fermentable carbon source. The system is capable of making as much as 15 mg of human interferon‐alpha per litre of batch culture.

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