A preclinical study demonstrated that CRISPR–Cas3, delivered by lipid nanoparticles, can generate directional, long‑range deletions at the TTR locus in mice, achieving ~48.7% hepatic editing and reducing serum transthyretin by roughly 80%. The authors reported mostly large deletions up to tens of kilobases without reproducible off‑target mutations, contrasting with Cas9’s indel profile and off‑target footprint. Investigators framed Cas3 as a mechanistically distinct in vivo genome‑editing tool that may lower the risk of residual in‑frame mutations and persistent protein expression. The work advances the therapeutic toolbox for transthyretin amyloidosis and highlights delivery, deletion control, and safety profiling as the next steps toward clinical translation.