Villiger, L. et al. Nat. Med. 24, 1519–1525 (2018)

Phenylketonuria (PKU) is a heritable disease caused by loss-of-function mutations to enzymes involved in liver cell metabolism. Special diets can help prevent symptoms in humans and adding the missing enzyme can treat the condition in PKU mouse models, but there is no cure. The genetic basis of the disease makes it a candidate for gene editing, but previous attempts to edit the mouse liver haven’t proved particularly efficient.

Base editing might be a more fruitful strategy, suggests new research from a team of Swiss researchers. Such approaches are able to change a base in a DNA sequence without having to break and the repair both strands, reducing potential off-target effects. The researchers delivered the base editor in two portions to the liver of adult mice modeling PKU via dual adeno-associated viral vectors and observed correction rates up to 63%.