High-dose systemic adeno-associated virus vector administration causes liver and sinusoidal endothelial cell injury.

ABSTRACT: We analyzed retrospective data from toxicology studies involving administration of high doses of adeno-associated virus expressing different therapeutic transgenes to 21 cynomolgus and 15 rhesus macaques. We also conducted prospective studies to investigate acute toxicity following high-dose systemic administration of enhanced green fluorescent protein-expressing adeno-associated virus to 10 rhesus macaques. Toxicity was characterized by transaminitis, thrombocytopenia, and alternative complement pathway activation that peaked on post-administration day 3. Although most animals recovered, some developed ascites, generalized edema, hyperbilirubinemia, and/or coagulopathy that prompted unscheduled euthanasia. Study endpoint livers from animals that recovered and from unscheduled necropsies o

SUBMITTER: Hordeaux J 

PROVIDER: S-EPMC11163197 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature