Nature Biotechnology‑published methods expanded base‑editing safety and targeting precision. One paper introduces CHANGE‑seq‑BE, a genome‑wide assay that sensitively maps base editor off‑target activity. A second study reports directed evolution of adenine base editors (ABEs) combined with 3′‑extended guide RNAs to reduce bystander edits and increase on‑target fidelity. CHANGE‑seq‑BE provides high‑resolution, unbiased detection of unintended edits, enabling developers to profile candidate editors before clinical translation. The improved ABEs reduce collateral editing in therapeutic windows where bystander mutations would be deleterious. Together, these advances strengthen preclinical assessment and engineering pathways for safer clinical base‑editing programs.