A Nature Biotechnology report shows a directed‑evolution campaign combined with extended guide RNAs produced adenine base editors with markedly improved precision and reduced bystander edits. The optimized editors retain on‑target efficiency while lowering unintended adenine conversions in adjacent bases. The authors present biochemical metrics, cellular editing profiles and comparisons across clinically relevant loci, arguing the improvements reduce a major barrier to therapeutic adoption of adenine base editing. The study supplies an engineering template for companies advancing base‑editor clinical programs to meet regulatory expectations for specificity.