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Herpes simplex virus thymidine kinase (HSV-TK) is an enzyme encoded by the herpes simplex virus type 1 (HSV-1) gene. It is a homodimeric α/β-protein that plays a key role in the viral nucleoside salvage pathway by phosphorylating natural nucleosides and various nucleoside analogs[2][6]. In gene therapy, particularly cancer suicide gene therapy, HSV-TK is widely used as a "suicide gene." When introduced into tumor cells and combined with prodrugs such as ganciclovir or acyclovir, HSV-TK phosphorylates these drugs to their active forms. The activated drugs then inhibit DNA synthesis in dividing cells, leading to selective cell death of transduced tumor cells[1][6][8]. This approach exploits the broad substrate specificity of HSV-TK for both pyrimidine and purine analogs. Mutant forms of HSV-TK have been engineered to enhance sensitivity to specific prodrugs or reduce toxicity[1][8]. Beyond oncology applications, HSV-TK has also been explored for regulating stem cell transplantation and treating certain infections[5].
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