Uprt-flox Mouse

Uprt, short for uracil phosphoribosyltransferase, is an enzyme in the pyrimidine salvage pathway. It catalyzes the conversion of uracil to uridine monophosphate (UMP), and is highly conserved across species from prokaryotes to humans [1].

In Drosophila, the Uprt homologue, krishah (kri), is essential for larval growth, pre-pupal/pupal viability, and long-term adult lifespan, suggesting that Uprt in higher eukaryotes likely has in-vivo enzymatic activity [1].

In gene therapy, Uprt is part of the CD/UPRT system. For example, vaccinia virus armed with CD/UPRT can convert 5-fluorocytosine (5-FC) into chemotherapeutic agents, showing anti-tumor effects against pancreatic ductal adenocarcinoma [2]. In glioma gene therapy, UPRT in the CD::UPRT/5-FC system can catalyze 5-fluorouracil (5-FU) to 5-fluorouridine monophosphate, which kills cells via the bystander effect [3]. Engineered oncolytic adenovirus expressing UPRT can enhance the toxicity of 5-FU, and cyclophosphamide can further improve its antitumor efficacy in immunocompetent Syrian hamsters [4]. Also, expressing AtUPRT from Arabidopsis thaliana in HeLa cells makes them more sensitive to 5-FU, leading to decreased cell viability, apoptosis, and cell cycle arrest [5].

In conclusion, Uprt plays a crucial role in pyrimidine metabolism and has significant implications in cancer gene therapy. Studies in model organisms like Drosophila and gene-therapy-related cell models have revealed its importance in growth, survival, and tumor-targeted treatment, highlighting its potential as a therapeutic target or tool in cancer treatment.