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**HSV-TK + ganciclovir** is a combination of **gene therapy** and **antiviral prodrug therapy** used primarily in experimental and investigational settings, most often as a form of suicide gene therapy for cancer and cell ablation. The therapy involves the introduction (typically via viral or other vectors) of the gene encoding herpes simplex virus thymidine kinase (HSV-TK) into target cells. HSV-TK is a viral enzyme that phosphorylates the nucleoside analogue ganciclovir (GCV), converting it into a monophosphate and subsequently, via cellular enzymes, into a cytotoxic triphosphate form. This triphosphate is then incorporated into cellular DNA, leading to chain termination and selective cell death. Because mammalian thymidine kinase does not efficiently phosphorylate GCV, only HSV-TK-expressing cells are sensitized to ganciclovir, enabling targeted ablation (the so-called "suicide effect"). The HSV-TK + ganciclovir system is also notable for the "bystander effect," whereby neighboring non-transduced cells may also be killed due to transfer of toxic metabolites, enhancing therapeutic efficacy[2][3][4][9][10].
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