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Correction of the ion transport defect in cystic fibrosis transgenic mice by gene therapy.
- Source :
-
Nature [Nature] 1993 Mar 18; Vol. 362 (6417), pp. 250-5. - Publication Year :
- 1993
-
Abstract
- 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.
- Subjects :
- Animals
Base Sequence
Chloride Channels
Colforsin pharmacology
Cyclic AMP metabolism
Cystic Fibrosis Transmembrane Conductance Regulator
Drug Carriers
Epithelial Cells
Epithelium drug effects
Epithelium pathology
Epithelium physiology
HeLa Cells
Humans
In Situ Hybridization
Liposomes
Mice
Mice, Transgenic
Oligonucleotide Probes
Plasmids
RNA, Messenger metabolism
Trachea pathology
Trachea physiopathology
Transfection
Cystic Fibrosis genetics
Cystic Fibrosis therapy
Genetic Therapy
Ion Channels physiology
Membrane Proteins genetics
Membrane Proteins physiology
Trachea physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0028-0836
- Volume :
- 362
- Issue :
- 6417
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 7681548
- Full Text :
- https://doi.org/10.1038/362250a0