Herpes simplex virus type 1 thymidine kinase (HSV1-TK) (HSV1-TK)

Herpes simplex virus type 1 thymidine kinase (HSV1-TK) is a viral enzyme widely used in gene-directed enzyme prodrug therapy (GDEPT), commonly known as suicide gene therapy (UniProt P03176). In the context of PA1STK-modified cells, the enzyme is expressed in the PA-1 human ovarian teratocarcinoma cell line to facilitate targeted cell destruction (PubMed: 10861918). The enzyme's primary therapeutic function is the phosphorylation of nucleoside analogs like ganciclovir, which are poor substrates for human kinases, into monophosphate intermediates (PubChem CID 3454). These intermediates are further processed by host cell kinases into cytotoxic triphosphates that inhibit DNA polymerase and trigger apoptosis. A significant advantage of this system is the bystander effect, where toxic metabolites pass to adjacent non-transduced cells through gap junctions, amplifying the anti-tumor response (PubMed: 10623510). HSV1-TK also serves as a reporter gene for molecular imaging, allowing for the non-invasive monitoring of gene expression using PET scans with specialized tracers like 18F-FHBG (PubMed: 15235058).

Other names

HSV-tkHerpes simplex virus thymidine kinaseSuicide gene TKViral thymidine kinasePA1STK-expressed TK

The enzyme mediates the phosphorylation of nucleoside analogs like ganciclovir into monophosphate forms, which are then converted by host cell kinases into toxic triphosphates that inhibit DNA polymerase and induce apoptosis (PubChem CID 3454).