PAH and phenylketonuria: ,22 When SpRY-ABE8.8/PAH4 base editing for correction of the PAH c.1222C>T variant is compared against a similar base editing approach for correction of the PAH c.842C>T (p.Pro281Leu) variant,9 also a frequent (albeit much less frequent) PKU variant, the former had substantially less potency in HuH-7 cells (EC50 of 750 fmol/cell versus EC50 of 64 fmol/cell), less editing activity in the mouse liver when delivered with the same LNP formulation at the same 2.5-mg/kg dose (mean desired on-target editing of 26% versus 39%), and more unwanted bystander editing in vivo (2.8% versus 0.8%).