Herpes simplex virus type 1 thymidine kinase sr39 mutant (HSV1-sr39tk) (HSV1-sr39tk)

Herpes simplex virus type 1 thymidine kinase sr39 mutant (HSV1-sr39tk) is an engineered enzyme used primarily in gene therapy and molecular imaging (Gambhir et al., 2000). It is a semi-random mutant of the wild-type HSV1-TK, featuring five amino acid substitutions (L159I, I160L, F161L, A168H, and L169M) that significantly increase its affinity for nucleoside analogs like ganciclovir while decreasing its affinity for endogenous thymidine (Black et al., 1996). In the context of suicide gene therapy, HSV1-sr39tk is delivered to target cells, where it phosphorylates administered prodrugs into monophosphate forms. These are subsequently converted by cellular kinases into cytotoxic triphosphates that inhibit DNA polymerase and cause cell death (Fillat et al., 2003). Beyond its role in oncology, this enzyme serves as a critical safety switch in adoptive T-cell therapies, allowing for the selective elimination of engineered cells in the event of severe toxicity (Ciceri et al., 2009). Additionally, its high affinity for specific radiolabeled reporters like [18F]FHBG makes it a gold-standard reporter gene for non-invasive positron emission tomography (PET) imaging of gene expression (Yaghoubi et al., 2006).

Other names

sr39TKHSV1-TK sr39Mutant herpes simplex virus type 1 thymidine kinaseSuicide gene HSV1-tk

The HSV1-sr39tk enzyme selectively phosphorylates nucleoside analog prodrugs into monophosphates; these are then converted by host kinases into triphosphates that act as DNA chain terminators, leading to apoptosis (Black et al., 1996; Fillat et al., 2003).