Herpes simplex virus type 1 thymidine kinase mutant SR39 (HSV-1 TK SR39)

Herpes simplex virus type 1 thymidine kinase mutant SR39 (HSV-1 TK SR39) is an engineered enzyme derived from the wild-type viral thymidine kinase by random mutagenesis, producing increased affinity and efficiency for phosphorylating antiviral prodrugs such as ganciclovir and acyclovir[1][2][3][5]. Wild-type HSV-1 thymidine kinase is a well-established enzyme in gene therapy strategies, particularly "suicide gene therapy" for cancer, because it efficiently phosphorylates nucleoside analogs that human thymidine kinase cannot utilize. Mutant SR39, among other engineered variants, displays superior kinetic parameters, including markedly lower Km (higher affinity) and increased specificity for ganciclovir—up to 80-fold higher than the wild-type enzyme—making it highly effective at converting non-toxic prodrugs into their cytotoxic form within targeted cancer cells, resulting in selective tumor cell death[1][3][5]. SR39 is commonly used in preclinical and clinical research to enhance the therapeutic index of suicide gene approaches, but its clinical use is constrained by the need to manage systemic toxicity of the prodrugs and the efficiency and specificity of vector-mediated gene delivery[1][2].

Other names

HSV-1 thymidine kinase SR39HSV TK SR39mutant SR39thymidine kinase SR39

Phosphorylation of prodrug nucleosides to active toxic metabolites, leading to DNA synthesis inhibition and selective cell death in target (e.g., tumor) cells expressing the enzyme