St. Jude researchers unveiled CHANGE‑seq‑BE, a genome‑wide, unbiased method to map off‑target activity induced by base editors. The approach prioritizes sensitivity and resource efficiency to provide safety data that can be used in clinical regulatory interactions. Authors reported a case application supporting an emergency FDA review for a base‑editor treatment of X‑linked hyper‑IgM syndrome; CHANGE‑seq‑BE confirmed ~95.4% on‑target specificity for the editor used with no significant off‑target activity detected. The team argues the assay helps select editor/target pairs with favorable safety profiles for therapeutic advancement. CHANGE‑seq‑BE may become a standard safety screen for translational base‑editing programs as developers seek robust genome‑wide evidence ahead of human dosing.