Researchers reported use of CRISPR–Cas3, a mechanistically distinct genome‑editing system that produces long‑range deletions, to target the transthyretin (TTR) locus in mice. Delivered via lipid nanoparticles, a single in vivo treatment achieved nearly 49% hepatic editing and reduced circulating TTR by about 80%, while producing directional deletions up to tens of kilobases with minimal reproducible off‑target edits. The work, published in Nature Biotechnology, positions Cas3 as an alternative to nuclease-induced indels for diseases where large deletions reduce residual mutant protein.