Journal article
Repeat administration of an adenovirus vector encoding cystic fibrosis transmembrane conductance regulator to the nasal epithelium of patients with cystic fibrosis
The Journal of clinical investigation, Vol.97(6), pp.1504-1511
03/15/1996
DOI: 10.1172/JCI118573
PMCID: PMC507211
PMID: 8617884
Abstract
Cystic fibrosis (CF) is a common autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator gene. Recombinant adenoviruses have shown promise as vectors for transfer of CF transmembrane conductance regulator cDNA to airway epithelia and correction of the Cl- transport defect. However, because adenovirus-mediated gene transfer is transient, use of adenovirus as a vector for treatment of CF would require repeated administration. Therefore, we evaluated repeat administration of an adenovirus vector to the nasal epithelium of patients with CF with five escalating doses of up to 10(10) infectious units. There were no detectable adverse affects. All subjects were initially seropositive but developed additional humoral immune responses. The vector partially corrected the defect in airway epithelial Cl- transport in some subjects, although there was variability between subjects and there was less correction with subsequent administration, perhaps because the immune response limited gene transfer. Future work must focus on vectors with increased efficiency and with the ability to evade host defenses.
Details
- Title: Subtitle
- Repeat administration of an adenovirus vector encoding cystic fibrosis transmembrane conductance regulator to the nasal epithelium of patients with cystic fibrosis
- Creators
- Joseph Zabner - Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, 52242, USABonnie W Ramsey - Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, 52242, USADavid P Meeker - Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, 52242, USAMoira L Aitken - Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, 52242, USARosemary Balfour - Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, 52242, USARonald L Gibson - Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, 52242, USAJan Launspach - Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, 52242, USARichard A Moscicki - Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, 52242, USASusan M Richards - Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, 52242, USAThomas A Standaert - Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, 52242, USAJudy Williams-Warren - University of WashingtonSamuel C WadsworthAlan E SmithMichael J Welsh - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.97(6), pp.1504-1511
- DOI
- 10.1172/JCI118573
- PMID
- 8617884
- PMCID
- PMC507211
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 03/15/1996
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Internal Medicine
- Record Identifier
- 9984020616202771
Metrics
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