A research team evaluated the CRISPR–Cas3 system for therapeutic genome editing to permanently reduce transthyretin (TTR) production, demonstrating a distinct mechanism compared with Cas9. The study—reported in Nature Biotechnology—shows Cas3’s processive nuclease activity can enable larger deletions and different editing outcomes that may benefit certain loss‑of‑function strategies. Authors argue Cas3 could offer an alternative path for diseases where permanent gene disruption is desirable, including hereditary transthyretin amyloidosis. The paper details preclinical performance and contrasts Cas3’s editing profile, highlighting both potential advantages and safety considerations relative to Cas9‑based approaches. Cas3 refers to a CRISPR effector with processive DNA degradation properties; unlike the precise cuts of Cas9, Cas3 can remove larger genomic segments, which has distinct therapeutic tradeoffs.