Researchers published a tailored pipeline, CHANGE-seq-BE, that profiles base-editor–induced off-target activity across genomes with high sensitivity. The method, reported in Nature Biotechnology, provides a genome-wide, unbiased catalogue of unintended edits from base editors used in preclinical and therapeutic settings. The lead development clarifies where base editors create collateral edits and gives developers actionable data to refine guide design and editor chemistry. In a separate paper, teams used directed evolution and 3′-extended guide RNAs to tighten adenine base editor (ABE) specificity. The work demonstrated reduced bystander editing and improved target selectivity in cell models, a key technical advance for clinical gene correction. Together, the assay and evolved ABEs create a short-term roadmap: measure off-target activity with high precision, then apply evolved editors and extended guides to reduce risk before clinical translation.