Systemic gene therapy using an AAV44.9 vector rescues a neonatal lethal mouse model of propionic acidemia.

ABSTRACT: Propionic acidemia (PA) is rare autosomal recessive metabolic disorder caused by defects in the mitochondrially localized enzyme propionyl-coenzyme A (CoA) carboxylase. Patients with PA can suffer from lethal metabolic decompensation and cardiomyopathy despite current medical management, which has led to the pursuit of gene therapy as a new treatment option for patients. Here we assess the therapeutic efficacy of a recently described adeno-associated virus (AAV) capsid, AAV44.9, to deliver a therapeutic PCCA transgene in a new mouse model of propionyl-CoA carboxylase α (PCCA) deficiency generated by genome editing. Pcca^-/- mice recapitulate the severe neonatal presentation of PA and manifest uniform neonatal lethality, absent PCCA expression, and increased 2-methyl

SUBMITTER: Chandler RJ 

PROVIDER: S-EPMC10512014 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature