The FDA has imposed a clinical hold on two Phase 3 trials of Intellia Therapeutics’ CRISPR candidate nexiguran ziclumeran (nex‑z) after a study participant developed a grade‑4 liver event that required hospitalization. Intellia had voluntarily paused dosing earlier in the week; the agency’s formal hold requires a written response within 30 days and could extend the pause by several quarters. Intellia said it will cooperate with the FDA and independent experts to develop new safety measures. The trials targeted transthyretin amyloidosis (ATTR) cardiomyopathy and polyneuropathy and had enrolled hundreds of patients; the cardiomyopathy study had over 650 participants. Analysts warn the regulatory hold raises scrutiny on on‑target toxicities for in vivo gene editing and may delay pivotal readouts. The episode adds to an intensifying industry debate over the safety profile of durable, once‑and‑done gene‑editing approaches and the regulatory bar for systemic genome editors. Companies developing in vivo editing and long‑acting genetic medicines will likely face increased FDA attention on hepatic monitoring and long‑term safety plans. For readers: the key regulatory step is that the FDA will issue a formal letter outlining required information and safety changes; sponsors must formally reply before resuming dosing. Expect investor and partner recalibrations while Intellia engages regulators.