Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2001-8-3
pubmed:abstractText
A phase I clinical trial was conducted in which recombinant adenovirus containing the cystic fibrosis trans-membrane regulator (CFTR) (Ad2/CFTR) was administered by bronchoscopic instillation or aerosolization to the lungs of cystic fibrosis (CF) patients. In this paper, we evaluate the efficiency of Ad2/CFTR-mediated transduction of bronchial airway cells. The ability of an Ad2/CFTR vector to transduce airway cells was first evaluated in patients to whom the vector was administered by bronchoscopic instillation. Cells at the administration site were collected 2 days after treatment by bronchoscopic brushing. Ad2-specific CFTR DNA was detected in four of five individuals by PCR, and Ad2-specific CFTR RNA was detected in three of five individuals by RT-PCR. Ad2/CFTR-mediated transduction of airway epithelial cells was then determined in CF individuals receiving this vector by aerosol inhalation. Ad2-specific CFTR DNA was detected in 13 of 13 individuals 2 days after aerosolization, and in 3 of 5 individuals 7 days after aerosolization. Ad2-specific RNA was detected in 4 of 13 individuals on day 2, but was not detected in the 5 individuals tested on day 7. The percentage of airway epithelial cells containing nuclear-localized vector DNA was < or =2.4% as determined by fluorescence in situ hybridization (FISH). However, in some cases, a high percentage of nonepithelial mononuclear cells or squamous metaplastic epithelial cells was infected with the adenoviral vector. In conclusion, aerosol administration is a feasible means to distribute adenoviral vectors throughout the conducting airways, but improvements in adenovirus-mediated transduction of airway epithelial cells are necessary before gene therapy for CF will be effective.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1043-0342
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1383-94
pubmed:dateRevised
2006-4-21
pubmed:meshHeading
pubmed-meshheading:11485630-Adenoviridae, pubmed-meshheading:11485630-Administration, Inhalation, pubmed-meshheading:11485630-Adolescent, pubmed-meshheading:11485630-Adult, pubmed-meshheading:11485630-Bronchoscopy, pubmed-meshheading:11485630-Cystic Fibrosis, pubmed-meshheading:11485630-Cystic Fibrosis Transmembrane Conductance Regulator, pubmed-meshheading:11485630-DNA, Recombinant, pubmed-meshheading:11485630-Female, pubmed-meshheading:11485630-Genetic Vectors, pubmed-meshheading:11485630-Humans, pubmed-meshheading:11485630-In Situ Hybridization, Fluorescence, pubmed-meshheading:11485630-Instillation, Drug, pubmed-meshheading:11485630-Male, pubmed-meshheading:11485630-Polymerase Chain Reaction, pubmed-meshheading:11485630-RNA, Messenger, pubmed-meshheading:11485630-Recombinant Proteins, pubmed-meshheading:11485630-Respiratory Mucosa, pubmed-meshheading:11485630-Time Factors, pubmed-meshheading:11485630-Transduction, Genetic, pubmed-meshheading:11485630-Transfection
pubmed:year
2001
pubmed:articleTitle
Aerosol and lobar administration of a recombinant adenovirus to individuals with cystic fibrosis. II. Transfection efficiency in airway epithelium.
pubmed:affiliation
Genzyme Corporation, Framingham, MA 01701, USA. michael. perricone@genyme.com
pubmed:publicationType
Journal Article, Clinical Trial, Multicenter Study, Clinical Trial, Phase I