Use of an adeno-associated virus serotype Anc80 to provide durable cure of phenylketonuria in a mouse model.

ABSTRACT: Phenylketonuria (PKU) is the most common inborn error of metabolism of the liver, and results from mutations of both alleles of the phenylalanine hydroxylase gene (PAH). As such, it is a suitable target for gene therapy via gene delivery with a recombinant adeno-associated virus (AAV) vector. Here we use the synthetic AAV vector Anc80 via systemic administration to deliver a functional copy of a codon-optimized human PAH gene, with or without an intron spacer, to the Pah^enu2 mouse model of PKU. Dose-dependent transduction of the liver and expression of PAH mRNA were present with both vectors, resulting in significant and durable reduction of circulating phenylalanine, reaching near control levels in males. Coat color of treated Pah^enu2 mice reflected an increase in pi

SUBMITTER: Kaiser RA 

PROVIDER: S-EPMC9291745 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature