hsv-tk

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. 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. 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. Beyond oncology applications, HSV-TK has also been explored for regulating stem cell transplantation and treating certain infections.