Repeated dosing of AAV-mediated liver gene therapy in juvenile rat and mouse models of Crigler-Najjar syndrome type I.

ABSTRACT: Crigler-Najjar syndrome is an ultra-rare monogenic recessive liver disease caused by UGT1A1 gene mutations. Complete UGT1A1 deficiency results in severe unconjugated hyperbilirubinemia in newborns that, if not treated, may lead to brain damage and death. Treatment is based on intensive phototherapy, but its efficacy decreases with age, rendering liver transplantation the only curative option. Adeno-associated virus (AAV)-mediated gene therapy has shown long-term correction in adult patients, but loss of viral DNA and therapeutic efficacy are expected in younger patients associated with liver growth. Effective vector re-administration is hindered by anti-AAV neutralizing antibodies generated during the first administration. Here, we investigated AAV vector re-administration by modula

SUBMITTER: Shi X 

PROVIDER: S-EPMC11607602 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature