The FDA placed clinical holds on two Phase 3 trials of Intellia Therapeutics’ in‑vivo CRISPR candidate nexiguran ziclumeran (nex‑z) after a grade‑4 adverse event—marked liver enzyme and bilirubin elevation—that hospitalized a participant. Intellia had voluntarily paused dosing earlier the week; the formal hold requires a written FDA letter within 30 days and a sponsor response before studies can resume. Intellia is developing nex‑z for transthyretin amyloidosis (ATTR) cardiomyopathy and polyneuropathy as a potentially durable, one‑time in‑vivo gene‑editing therapy. The regulatory hold raises questions about the monitoring, risk‑mitigation and patient selection strategies required for systemic in‑vivo CRISPR therapeutics. Investors reacted negatively, and analysts forecast several‑quarter delays to readouts. The episode underscores how safety signals in first‑in‑class gene‑editing programs can trigger intensified regulatory scrutiny; sponsors working on in‑vivo editing must now prepare more robust hepatic monitoring and mitigation plans.