Mutated cytosine deaminase (CD) (CD)

Mutated cytosine deaminase is an engineered enzyme, typically derived from Saccharomyces cerevisiae (yeast) or Escherichia coli, designed for use in gene-directed enzyme prodrug therapy (GDEPT) for cancer. While the wild-type enzyme naturally converts cytosine to uracil, the mutated versions are optimized for higher thermal stability and increased affinity for the prodrug 5-fluorocytosine (5-FC) (UniProt P25334). When the gene encoding this enzyme is delivered to tumor cells—often via a viral vector like Vocimagene amiretrorepvec—it facilitates the local conversion of 5-FC into the potent chemotherapeutic 5-fluorouracil (5-FU) (PMID: 27252444). This localized production of 5-FU creates a high concentration of the toxin within the tumor microenvironment, leading to the inhibition of thymidylate synthase and subsequent cell death (PubChem CID 3366). A key advantage of this system is the bystander effect, where 5-FU diffuses to neighboring non-transduced cancer cells, enhancing the overall anti-tumor response while minimizing systemic side effects (PMID: 11502023). This approach has been primarily investigated for the treatment of high-grade gliomas and other solid tumors.

Other names

yCDbCDcodAFCY1Cytosine aminohydrolaseVocimagene amiretrorepvec (gene component)Mutated yeast cytosine deaminase

The enzyme catalyzes the hydrolytic deamination of the non-toxic prodrug 5-fluorocytosine (5-FC) into the active cytotoxic agent 5-fluorouracil (5-FU), which subsequently inhibits thymidylate synthase and disrupts DNA and RNA synthesis, leading to cell death.