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

• Published in: Nature (London) 1993-03, Vol.362 (6417), p.250-255
• Main Authors: Hyde, Stephen C, Gill, Deborah R, Higgins, Christopher F, Trezise, Ann E. O, MacVinish, Lesley J, Cuthbert, Alan W, Ratcliff, Rosemary, Evans, Martin J, Colledge, William H
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Biological and medical sciences; Chloride Channels; Colforsin - pharmacology; Cyclic AMP - metabolism; Cystic fibrosis; Cystic Fibrosis - genetics; Cystic Fibrosis - therapy; Cystic Fibrosis Transmembrane Conductance Regulator; Drug Carriers; Epithelial Cells; Epithelium - drug effects; Epithelium - pathology; Epithelium - physiology; Gastroenterology. Liver. Pancreas. Abdomen; Genetic Therapy; Genetics; HeLa Cells; Humanities and Social Sciences; Humans; In Situ Hybridization; Ion Channels - physiology; Ion transport; letter; Liposomes; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Medical research; Medical sciences; Membrane Proteins - genetics; Membrane Proteins - physiology; Mice; Mice, Transgenic; multidisciplinary; Oligonucleotide Probes; Other diseases. Semiology; Plasmids; RNA, Messenger - metabolism; Rodents; Science; Science (multidisciplinary); Trachea - pathology; Trachea - physiology; Trachea - physiopathology; Transfection
• ISSN: 0028-0836; 1476-4687
• 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 1 that encodes a cyclic-AMP-regulated chloride channel 2,3 . Cyclic-AMP-regulated chloride conductances are altered in airway epithelia from CF patients 4–6 , suggesting that the functional expression of CFTR in the airways of CF patients may be a strategy for treatment. Transgenic mice 7–9 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.