Use of an oversized AAV8 vector for CPS1 deficiency results in long-term survival and ammonia control.

ABSTRACT: Carbamoyl phosphate synthetase 1 (CPS1) deficiency, a urea-cycle disorder, results in hyperammonemia initiating a sequence of adverse events that can lead to coma and death if not treated rapidly. There is a high unmet need for an effective therapeutic for this disorder, especially in early neonatal patients where mortality is excessive. However, development of an adeno-associated virus (AAV)-based approach is hampered by large cDNA size and high protein requirement. We developed an oversized AAV vector as a gene therapy to treat CPS1 deficiency. In order to constrain genome size, we utilized small liver-specific promoter/enhancers and a minimal polyadenylation signal. Long-term survival (9 months, end of study) with ammonia control was achieved in AAV8.CPS1-administered Cps1^fl

SUBMITTER: Diep T 

PROVIDER: S-EPMC11905892 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature