Gene Transfer to Cystic Fibrosis Airway Epithelia

Cationic lipids show promise as vectors for transfer of CFTR cDNA to airway epithelia of patients with cystic fibrosis (CF). However, previous studies have not compared the effect of DNA–lipid to DNA alone. Recently, we developed a formulation of plasmid encoding CFTR (pCF1CFTR) and cationic lipid (GL-67:DOPE) that generated greater gene transfer in mouse lung than previously described DNA–lipid vectors. Therefore, we tested the hypothesis that DNA–lipid complexes were more effective than DNA alone at transferring CFTR cDNA to airway epithelia in vivo. We administered complexes of DNA–lipid to one nostril and DNA alone to the other nostril in a randomized, double-blind study. Electrophysiologic measurements showed that DNA–lipid complexes partially corrected the Cl 2 transport defect. Importantly, the pCF1-CFTR plasmid alone was at least as effective as complexes of DNA with lipid. Measurements of vector-specific CFTR transcripts also showed gene transfer with both DNA–lipid and DNA alone. These results indicate that nonviral vectors can transfer CFTR cDNA to airway epithelia and at least partially restore the Cl 2 transport defect characteristic of CF. However, improvements in the overall efficacy of gene transfer are required to develop a treatment for CF. ( J. Clin. Invest. 1997. 100:1529–1537.)