Adenine base editing of common mutation in PAH for phenylketonuria

Lipid nanoparticle delivery of an adenine base editor that corrects a C-to-T point mutation in the phenylalanine-clearing enzyme PAH, which is common among phenylketonuria patients, could help treat the disease.

In a human hepatocyte cell line bearing the mutation, screening of a panel of adenine base editors and guide RNAs for maximal on-target A-to-G editing on the antisense strand, and minimal off-target editing, identified an ABE8.8 editor and two guide RNAs that achieved corrective editing without bystander editing on ~50% of the alleles...