Transfer of Suicide Genes

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Another gene therapy strategy involves the transduction of tumor cells with a gene capable of converting a nontoxic compound into a toxic metabolite. The two most commonly used genes for this are the herpes simplex thymidine kinase gene (HSV-tk) and the cytosine deaminase gene. HSV- tk that convert non-toxic ganciclovir to a cytotoxic triphosphate metabolite, and cytosine deaminase converts 5-fluorocytosine to the cyto-toxic antimetabolite 5-fluorouracil. This strategy could potentially lead not only to the killing of the transduced cells, but also to the killing of adjacent cells in a "bystander effect" so that only a fraction of the targeted cells are needed to be transduced for eradication of the tumor (3). Potential limitations with the transfer of suicide genes include toxicity to normal cells that are transduced at the same time. These problems may be addressed by gene transfer strategies, that selectively target tumor tissue. One strategy to selectively target lung cancer cells involves the transfer of HSV-tk with a carcino-

embryonic antigen (CEA) promoter because many lung cancer cells overexpress CEA. HSV- tk would then be selectively translated in CEA-overexpressing lung cancer cells.

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