Nature: FDA's Plausible Mechanism Pathway Could Scale Personalized CRISPR from Individual Patients to Thousands

Nature publishes a major news feature examining how the FDA's newly enacted Plausible Mechanism Pathway (issued in draft guidance in February 2026) could transform the regulatory landscape for individualized gene editing therapies. The pathway, inspired by the landmark Baby KJ case — in which a personalized CRISPR base editing therapy was designed and delivered in record time for an infant with a life-threatening ultra-rare enzyme deficiency — allows accelerated approval based on demonstration of plausible biological mechanism rather than requiring large randomized controlled trials. The feature examines Children's Hospital of Philadelphia's (CHOP) plan to launch a platform clinical trial system that could allow N-of-1 personalized CRISPR therapies for ultra-rare diseases to be extended systematically to thousands of patients. CHOP's researchers argue that their manufacturing and clinical infrastructure, combined with the regulatory precedent now established, could enable dozens of bespoke gene editing therapies annually. The piece notes that over 300 million people globally live with rare diseases, the vast majority of which have no approved treatment — and CRISPR's ability to be reprogrammed to any target makes it the natural platform for addressing this unmet need at scale.