Researchers applying CRISPR–Cas3 achieved substantial targeted deletions at the TTR locus and robust reductions in circulating transthyretin in mouse models. A single lipid‑nanoparticle delivery produced ~48.7% hepatic editing and an ~80% drop in serum TTR, with directional deletions and limited reproducible off‑target mutations reported versus Cas9. In humanized TTR mice Cas3 editing reduced serum TTR and attenuated macrophage‑associated deposition, positioning Cas3 as an alternative genome‑editing modality that generates long deletions to avoid residual in‑frame mutations.