Linked Life Data

10918483

Source:http://linkedlifedata.com/resource/pubmed/id/10918483

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2000-8-21
pubmed:abstractText
The major cause of mortality in patients with cystic fibrosis (CF) is lung disease. Expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene product in the airways is a potential treatment. Clinical studies in which the CFTR cDNA was delivered to the respiratory epithelia of CF patients have resulted in modest, transient gene expression. It seems likely that repeated administration of the gene transfer vector will be required for long-term gene expression. We have undertaken a double-blinded study in which multiple doses of a DNA/liposome formulation were delivered to the nasal epithelium of CF patients. Ten subjects received plasmid DNA expressing the CFTR cDNA complexed with DC-Chol/DOPE cationic liposomes, whilst two subjects received placebo. Each subject received three doses, administered 4 weeks apart. There was no evidence of inflammation, toxicity or an immune response towards the DNA/liposomes or the expressed CFTR. Nasal epithelial cells were collected 4 days after each dose for a series of efficacy assays including quantitation of vector-specific DNA and mRNA, immunohistochemistry of CFTR protein, bacterial adherence, and detection of halide efflux ex vivo. Airway ion transport was also assessed in vivo by repeated nasal potential difference (PD) measurements. On average, six of the treated subjects were positive for CFTR gene transfer after each dose. All subjects positive for CFTR function were also positive for plasmid DNA, plasmid-derived mRNA and CFTR protein. The efficacy measures suggest that unlike high doses of recombinant adenoviral vectors, DNA/liposomes can be successfully re-administered without apparent loss of efficacy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0969-7128
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1156-65
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10918483-Adolescent, pubmed-meshheading:10918483-Adult, pubmed-meshheading:10918483-Bacterial Adhesion, pubmed-meshheading:10918483-Cholesterol, pubmed-meshheading:10918483-Cystic Fibrosis, pubmed-meshheading:10918483-Cystic Fibrosis Transmembrane Conductance Regulator, pubmed-meshheading:10918483-Double-Blind Method, pubmed-meshheading:10918483-Epithelium, pubmed-meshheading:10918483-Female, pubmed-meshheading:10918483-Gene Expression, pubmed-meshheading:10918483-Gene Therapy, pubmed-meshheading:10918483-Genetic Vectors, pubmed-meshheading:10918483-Humans, pubmed-meshheading:10918483-Immunohistochemistry, pubmed-meshheading:10918483-Liposomes, pubmed-meshheading:10918483-Male, pubmed-meshheading:10918483-Nasal Mucosa, pubmed-meshheading:10918483-Phosphatidylethanolamines, pubmed-meshheading:10918483-Treatment Outcome
pubmed:year
2000
pubmed:articleTitle
Repeat administration of DNA/liposomes to the nasal epithelium of patients with cystic fibrosis.
pubmed:affiliation
Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, UK.
pubmed:publicationType
Journal Article, Clinical Trial, Randomized Controlled Trial, Research Support, Non-U.S. Gov't