Novel Gene Editing Approach for Treating Cystic Fibrosis

A novel genetic-editing approach for the systemic treatment of cystic fibrosis (CF) is reported in Science Advances this week. While efforts to develop gene therapies for CF — a condition caused by mutations in the CF transmembrane conductance regulator (CFTR) gene — have been underway for years, they have all faced challenges delivering their therapeutic payloads to affected organs including the lung and gastrointestinal (GI) tract. Aiming to overcome this issue, Yale University scientists developed a non-nuclease-based approach to gene editing by using endogenous DNA repair stimulated by the binding of peptide nucleic acids (PNAs) to genomic DNA to create PNA/DNA/PNA triplexes that can initiate an endogenous DNA repair response. When PNAs are introduced with a single-stranded donor DNA containing the desired sequence modification, site-specific modification of the genome occurs. The researchers show that PNAs designed to correct a common CF-causing mutation can be delivered systemically using biocompatible polymeric nanoparticles into mouse models of CF, triggering a partial gain of CFTR function in both airway and GI tissues with no off-target effects. The work, the study's authors write, lays the foundation for systemic in vivo gene editing to correct CF.