Comparison of DNA-lipid complexes and DNA alone for gene transfer to cystic fibrosis airway epithelia in vivo

J Clin Invest. 1997 Sep 15;100(6):1529-37. doi: 10.1172/JCI119676.


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 (pCF1-CFTR) 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- 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- transport defect characteristic of CF. However, improvements in the overall efficacy of gene transfer are required to develop a treatment for CF.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Amiloride / pharmacology
  • Chlorine / pharmacology
  • Cystic Fibrosis / metabolism
  • Cystic Fibrosis / therapy*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / immunology
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • DNA / administration & dosage*
  • DNA / immunology
  • DNA / pharmacokinetics
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Evaluation Studies as Topic
  • Female
  • Gene Transfer Techniques*
  • Genetic Vectors
  • Humans
  • Interleukin-6 / blood
  • Lipids / immunology
  • Lipids / pharmacokinetics
  • Male
  • Membrane Potentials / drug effects
  • Middle Aged
  • Nasal Mucosa / drug effects
  • Nasal Mucosa / metabolism*
  • Nasal Mucosa / physiology
  • Polymerase Chain Reaction
  • Terbutaline / pharmacology
  • Time Factors
  • Treatment Outcome


  • CFTR protein, human
  • Interleukin-6
  • Lipids
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Chlorine
  • Amiloride
  • DNA
  • Terbutaline