title: Adenovirus-mediated gene transfer transiently corrects the chloride transport defect in nasal epithelia of patients with cystic fibrosis.
abstract: To evaluate the potential of direct transfer of cystic fibrosis transmembrane conductance regulator (CFTR) cDNA for the treatment of cystic fibrosis (CF), we administered an E1-deficient adenovirus, encoding CFTR, to a defined area of nasal airway epithelium of three individuals with CF. This treatment corrected the Cl- transport defect that is characteristic of CF-affected epithelia. After treatment, there was a decrease in the elevated basal transepithelial voltage, and the normal response to a cAMP agonist was restored. We found no evidence of viral replication or virus-associated adverse effects, even at the highest dose tested (25 MOI). These data represent a small step in achieving long-term improvement of CF lung function by gene therapy.
authors.affiliation: Howard Hughes Medical Institute, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
authors.forename: J
authors.initials: J
authors.lastname: Zabner
authors.forename: L A
authors.initials: LA
authors.lastname: Couture
authors.forename: R J
authors.initials: RJ
authors.lastname: Gregory
authors.forename: S M
authors.initials: SM
authors.lastname: Graham
authors.forename: A E
authors.initials: AE
authors.lastname: Smith
authors.forename: M J
authors.initials: MJ
authors.lastname: Welsh
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D000584:Amiloride / Q000494:pharmacology; D001692:Biological Transport; D002712:Chlorides / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000235:genetics / Q000628:therapy*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004848:Epithelium / Q000378:metabolism; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism* / Q000473:pathology; D012449:Safety; D013726:Terbutaline / Q000494:pharmacology
chemical_list: C505032:CFTR protein, human; D002712:Chlorides; D008565:Membrane Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000584:Amiloride; D013726:Terbutaline