Researchers at St. Jude developed CHANGE‑seq‑BE, an unbiased, sensitive method to profile genome‑wide off‑target activity of CRISPR base editors to support safety evaluation in therapeutic settings. Separately, a CRISPR–Cas3 editing study demonstrated efficient, large directional deletions at the TTR locus in vitro and in mice, achieving about an 80% reduction in serum TTR with a single LNP‑delivered dose. Together the papers advance distinct genome‑editing toolsets: one enabling high‑resolution safety profiling for precise base editors and the other showcasing Cas3’s capacity for long deletions as a therapeutic strategy for transthyretin amyloidosis. Both works provide new preclinical evidence that could inform translational editing programs and regulatory review of in vivo genome‑editing approaches.