Grant: Project Grant

Cystic fibrosis (CF) is a devastating genetic disease affecting over 70,000 people worldwide. The disease is caused by mutations in the CFTR gene, which impede proper localization and compromise its essential function, particularly in the lungs, leading to severe morbidity and early mortality. Approximately 11% of CF patients carry genetic mutations that result in the production of truncated, non-functional, or partially functional CFTR proteins. The current drugs used to treat this class of CF mutations (called nonsense mutations) have limitations, making safe and efficient therapeutic strategies for CF nonsense mutations an urgent unmet clinical need. To address this unmet need, the proposed project aims to develop a novel therapeutic approach by delivering genetic editors to the lung using inhalable lipid nanoparticles. This approach is expected to cure CF patients by directly correcting CFTR nonsense mutations in the tissue most affected: the lungs. The project will first optimize the drug to produce maximal on-target editing of lung cells while minimizing off-target effects on other non-affected tissues. Then, the safety and efficacy of the lead drug candidates will be tested in a CFTR nonsense mutation mouse model. The research team brings together multidisciplinary expertise, including RNA biology, gene editing, lipid nanoparticle technology, and CF research, to address the project's challenges. If successful, this project has the potential to significantly advance the field of gene editing and provide a new treatment strategy for CF patients with nonsense mutations, representing a crucial step toward addressing an unmet medical need for CF patients and bringing hope to tens of thousands of affected individuals.