circCDUPRT

circCDUPRT is an engineered circular RNA (circRNA) designed for gene-directed enzyme prodrug therapy (GDEPT). It encodes a fusion protein consisting of cytosine deaminase (CD) and uracil phosphoribosyltransferase (UPRT). Delivered intratumorally via lipid nanoparticles (LNPs), the circRNA provides sustained expression of the CDUPRT enzyme within the tumor microenvironment. This enzyme facilitates the conversion of the non-toxic prodrug 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU) and its subsequent toxic metabolites, inducing localized tumor cell death while minimizing systemic side effects. Preclinical studies in melanoma models have demonstrated that circCDUPRT, especially when combined with IL-15-expressing circRNA, can significantly enhance the activation and expansion of CD8+ T cells and NK cells, offering a potent strategy for combined chemo-immunotherapy.

Other names

circular RNA encoding cytosine deaminase–uracil phosphoribosyltransferase