METABOLIC SUICIDE GENES IN GENE-THERAPY

This article reviews uses of metabolic suicide genes in gene therapy. Suicide genes encode novel nonmammalian enzymes that can convert a rel atively nontoxic prodrug into a highly toxic agent. Cells genetically transduced to express such genes essentially commit metabolic suicide in the presence of the appropriate prodrug. Three metabolic suicide ge nes are described: herpes simplex thymidine kinase, Escherichia coli c ytosine deaminase and varicella tester thymidine kinase. Transfer and expression of these genes into mammalian cells is described. Preclinic al models of suicide gene therapy of cancer and human immunodeficiency virus are discussed, and several clinical trials employing suicide ge nes are described.