Article Addendum www.landesbioscience.com rare diseases e27112-1 rare diseases 1, e27112; 2013; © 2013 landes Bioscience Article Addendum

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CFTR mutations lead to production of non-functional CFTR, reduced amounts of normal functioning CFTR or misfolded CFTR with defects in trafficking or function. For decades, CF treatment has been focused on the symptoms of CF, but pharmacotherapy using small molecules that target the basic defect of CF, the mutant CFTR pro-tein, is now possible for a limited amount of subjects with CF. This raises the excit-ing possibility that the majority of people with CF may receive effective treatment targeting the different CFTR mutants in the future. We recently described a func-tional CFTR assay using rectal biopsies from subjects with CF that were cultured in vitro into self-organizing mini-guts or organoids. We here describe how this model may assist in the discovery of new CFTR-targeting drugs, the subjects that may benefit from these drugs, and the mechanisms underlying variability in CFTR genotype-phenotype relations