Amelioration of metabolic and behavioral defects through base editing in a novel phenylketonuria mouse model

Phenylketonuria (PKU) is a liver metabolic disorders mainly caused by a deficiency of the hepatic phenylalanine hydroxylase (PAH) enzyme activity, often leading to severe brain function impairment in patients if untreated or if treatment is delayed. In this study, we utilized dual-AAV8 vectors to deliver a near PAM-less adenine base editor variant, known as ABE8e-SpRY, to treat a PKU mouse model carrying a frequent R408W mutation in the Pah gene.