Genome editing without nucleases confers proliferative advantage to edited hepatocytes and corrects Wilson disease.

ABSTRACT: Application of classic liver-directed gene replacement strategies is limited in genetic diseases characterized by liver injury due to hepatocyte proliferation, resulting in decline of therapeutic transgene expression and potential genotoxic risk. Wilson disease (WD) is a life-threatening autosomal disorder of copper homeostasis caused by pathogenic variants in copper transporter ATP7B and characterized by toxic copper accumulation, resulting in severe liver and brain diseases. Genome editing holds promise for the treatment of WD; nevertheless, to rescue copper homeostasis, ATP7B function must be restored in at least 25% of the hepatocytes, which surpasses by far genome-editing correction rates. We applied a liver-directed, nuclease-free genome editing approach, based on adeno-associated vi

SUBMITTER: Padula A 

PROVIDER: S-EPMC10721260 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature