title: Repeat administration of an adenovirus vector encoding cystic fibrosis transmembrane conductance regulator to the nasal epithelium of patients with cystic fibrosis.
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.
authors.affiliation: Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, 52242, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zabner
authors.forename: B W
authors.initials: BW
authors.lastname: Ramsey
authors.forename: D P
authors.initials: DP
authors.lastname: Meeker
authors.forename: M L
authors.initials: ML
authors.lastname: Aitken
authors.forename: R P
authors.initials: RP
authors.lastname: Balfour
authors.forename: R L
authors.initials: RL
authors.lastname: Gibson
authors.forename: J
authors.initials: J
authors.lastname: Launspach
authors.forename: R A
authors.initials: RA
authors.lastname: Moscicki
authors.forename: S M
authors.initials: SM
authors.lastname: Richards
authors.forename: T A
authors.initials: TA
authors.lastname: Standaert
mesh_terms: D000256:Adenoviridae; D000328:Adult; D003550:Cystic Fibrosis / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D004848:Epithelium / Q000378:metabolism; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000378:metabolism*
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator