CFTR and cystic fibrosis: In 1993, a pioneer study intended to compensate for defective CFTR in the nasal airway via gene replacement using an E1-deleted recombinant adenoviral (rAd) vector to deliver a normal copy of CFTR complementary DNA (cDNA) to the nasal epithelium of three patients with CF. Albeit not placebo-controlled, this study demonstrated proof-of-concept for gene therapy; specifically, for the transient correction of Cl− transport after vector inoculation (Zabner et al., 1993).