Pulmonary delivery of circular RNA therapeutics for cystic fibrosis

Cystic fibrosis (CF) is a life-threatening genetic disorder caused by CFTR mutations, leading to defective chloride transport and severe lung disease. Current CFTR modulator therapies benefit ~70% of patients but have limitations, including adverse effects and poor efficacy in ~10% of cases. Gene therapy offers a promising alternative, yet mRNA-based approaches suffer from instability. We developed a lipid nanoparticle (LNP)-delivered circRNA-CFTR therapy with superior stability and long-lasting CFTR expression, restoring chloride transport in CF models, offering a novel treatment strategy.