Modular Assembly Retroviral Vectors and Uses Therefor

Inventors: Fred H. Gage and Steven T. Suhr
Potential Uses: Gene Expression/Gene Therapy
Gene transfer vectors with the capacity for prolonged or modulated transgene expression

This invention relates to novel retroviral vectors containing modified long terminal repeats (LTR) which enable high level and ligand-modulatable expression of a desired gene product, even after prolonged periods of cellular quiescence. These novel vectors overcome proviral transcriptional inactivation which occurs in cultured primary cells that are growth arrested due to environmental constraints such as contact inhibition and/or nutrient starvation. These vectors represent a class of retroviral vectors in which LTR-promoted proviral expression in infected cells may be maintained or increased, even in situations generally considered to be non-permissive for retroviral vectors. This invention can be applied: as gene transfer vectors with the capacity for prolonged or modulated transgene expression for either in vivo or ex vivo gene therapy; as gene transfer vectors for efficient production of transgenic animals; as vectors for efficient gene transfer to developing embryos; and as vectors with inducible high titers.