A One-Time Genetic Cure for Cystic Fibrosis: Prime Editing + Basal-Cell Targeting

Abstract: Cystic fibrosis (CF) remains incurable despite highly effective modulators. Here we present an open-source, public-domain roadmap for a one-time genetic cure using prime editing delivered by nebulized, mucus-penetrating lipid nanoparticles that target airway basal stem cells. Integrating 2024-2025 breakthroughs, including up to 58% prime-editing efficiency for F508del in human airway organoids, 70% basal-cell editing with >660-day durability in CF ferret models, and hotspot correction of Class I nonsense mutations, we outline a detailed 5-year plan from current preclinical data to global approval by 2030. All concepts, methods, and timelines are released under CC-0 1.0 to block patenting and ensure universal, affordable access.