Gene Therapy in Cystic Fibrosis

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CF transmembrane regulator (CFTR) gene and is the most common life-shortening genetic defect in Caucasians. Life expectancy in CF has improved substantially during the past 75. years because of treatments aimed at end-organ complications. Since the CFTR gene was discovered in 1989, more than 1900 mutations have been reported to cause CF, and significant effort has been put forth into gene therapy to find a mutation-independent "cure" for CF. Gene-based approaches have not yet led to a viable therapy but have provided insights into hurdles that limit the efficacy and tolerability of gene therapy. This chapter will address the nomenclature of CFTR mutations, attempts at viral and nonviral gene therapy, and recent advances in mutation-specific protein repair molecules.