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 relatively 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 genes are described: herpes simplex thymidine kinase, Escherichia coli cytosine deaminase and varicella zoster thymidine kinase. Transfer and expression of these genes into mammalian cells is described. Preclinical models of suicide gene therapy of cancer and human immunodeficiency virus are discussed, and several clinical trials employing suicide genes are described.
Mullen
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Division of Cancer Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
D000818:Animals; D002986:Clinical Trials as Topic; D043525:Cytosine Deaminase; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D005798:Genes, Bacterial; D005814:Genes, Viral; D015316:Genetic Therapy; D015658:HIV Infections / Q000628:therapy*; D006561:Herpes Simplex / Q000201:enzymology / Q000235:genetics; D014645:Herpesvirus 3, Human / Q000201:enzymology / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000628:therapy*; D009700:Nucleoside Deaminases / Q000235:genetics*; D013937:Thymidine Kinase / Q000235:genetics*
D013937:Thymidine Kinase; D009700:Nucleoside Deaminases; D043525:Cytosine Deaminase