Gene therapy for cystic fibrosis: Progress and challenges of genome editing

Since the early days of its conceptualization and application, human gene transfer held thepromise of a permanent solution to genetic diseases including cystic fibrosis (CF). This field wentthrough alternated periods of enthusiasm and distrust. The development of refined technologiesallowing site specific modification with programmable nucleases highly revived the gene therapyfield. CRISPR nucleases and derived technologies tremendously facilitate genome manipulationoffering diversified strategies to reverse mutations. Here we discuss the advancement of gene therapy,from therapeutic nucleic acids to genome editing techniques, designed to reverse genetic defects inCF. We provide a roadmap through technologies and strategies tailored to correct different types ofmutations in the cystic fibrosis transmembrane regulator (CFTR) gene, and their applications for thedevelopment of experimental models valuable for the advancement of CF therapies.