New Retroviral Models for Gene Therapy: Swords into Plowshares

Retroviral-mediated gene transfer methods have been used to express the mouse nerve growth factor (NGF) gene in the rat brain and the retinoblastoma (RB) gene in retinoblastoma and osteosarcoma tumor cells. In both cases, transgene expression was accompanied by phenotypic changes in the target cells and organ. Established 208F rat fibroblasts expressing the NGF transgene and secreting active NGF were able to bring about the protection of cholinergic neurons in the fimbria fornix-lesioned rat brain, and retinoblastoma and osteosarcoma cells expressing the RB transgene showed normalized morphology and growth characteristics and failed to produce tumors when implanted into nude mice. These results indicate that genetic modification of appropriate target cells may be useful in the treatment of some CNS disorders and some kinds of cancer.