Correction of the ion transport defect in cystic fibrosis transgenic mice by gene therapy

Nature. 1993 Mar 18;362(6417):250-5. doi: 10.1038/362250a0.


Cystic fibrosis (CF) is a lethal inherited disorder affecting about 1 in 2,000 Caucasians. The major cause of morbidity is permanent lung damage resulting from ion transport abnormalities in airway epithelia that lead to mucus accumulation and bacterial colonization. CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that encodes a cyclic-AMP-regulated chloride channel. Cyclic-AMP-regulated chloride conductances are altered in airway epithelia from CF patients, suggesting that the functional expression of CFTR in the airways of CF patients may be a strategy for treatment. Transgenic mice with a disrupted cftr gene are appropriate for testing gene therapy protocols. Here we report the use of liposomes to deliver a CFTR expression plasmid to epithelia of the airway and to alveoli deep in the lung, leading to the correction of the ion conductance defects found in the trachea of transgenic (cf/cf) mice. These studies illustrate the feasibility of gene therapy for the pulmonary aspects of CF in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Chloride Channels
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis / therapy*
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Drug Carriers
  • Epithelial Cells
  • Epithelium / drug effects
  • Epithelium / pathology
  • Epithelium / physiology
  • Genetic Therapy*
  • HeLa Cells
  • Humans
  • In Situ Hybridization
  • Ion Channels / physiology*
  • Liposomes
  • Membrane Proteins / genetics*
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Transgenic
  • Oligonucleotide Probes
  • Plasmids
  • RNA, Messenger / metabolism
  • Trachea / pathology
  • Trachea / physiology*
  • Trachea / physiopathology
  • Transfection


  • CFTR protein, human
  • Chloride Channels
  • Drug Carriers
  • Ion Channels
  • Liposomes
  • Membrane Proteins
  • Oligonucleotide Probes
  • RNA, Messenger
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Colforsin
  • Cyclic AMP