AAV9-pMpz-CD::UPRT

AAV9-pMpz-CD::UPRT is an investigational gene therapy designed for the targeted treatment of schwannomas, particularly in the context of Neurofibromatosis Type 2 (NF2) and related schwannomatosis. The therapy utilizes an adeno-associated virus serotype 9 (AAV9) vector to deliver a suicide gene fusion construct consisting of cytosine deaminase (CD) and uracil phosphoribosyltransferase (UPRT). Expression of this fusion protein is specifically driven in Schwann cells by the myelin protein zero (Mpz) promoter. This approach is a form of gene-directed enzyme prodrug therapy (GDEPT); when the non-toxic prodrug 5-fluorocytosine (5-FC) is administered, the CD enzyme converts it into the chemotherapeutic agent 5-fluorouracil (5-FU), which is then further converted by UPRT into toxic metabolites like 5-fluorouridine monophosphate (5-FUMP). This localized conversion leads to the selective destruction of tumor cells while minimizing systemic side effects.

Other names

AAV9-Mpz-CD-UPRTAAV-9-Mpz-CD-UPRTAAV 9-Mpz-CD-UPRTAAV9-Mpz-CD::UPRT