Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1999-9-23
pubmed:abstractText
Gene transfer to the respiratory epithelium is currently suboptimal and may be helped by the identification of limiting biological barriers. We have, therefore, developed an ex vivo model which retains many of the characteristics of in vivo native airways including mucociliary clearance, mucus coverage and an intact cellular structure. Using this model we have demonstrated several barriers to gene transfer. Liposome-mediated gene transfer was inhibited by normal mucus, with removal of this layer increasing expression approximately 25-fold. In addition both liposome and adenovirus were inhibited by CF sputum. The apical membrane represented a significant barrier to both agents. Adenovirus-mediated expression could be significantly augmented by increasing contact time or by pre-treatment of tissues with a nominally calcium-free medium. The presence of these extracellular and plasma membrane barriers appeared to be the key parameters responsible for the approximately three log difference in gene expression found in vitro compared with our ex vivo model. Cytoskeletal elements and the cell cycle also influenced in vitro gene transfer, and represent further barriers which need to be overcome.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0969-7128
pubmed:author
pubmed:issnType
Print
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
534-46
pubmed:dateRevised
2009-9-29
pubmed:meshHeading
pubmed-meshheading:10476213-Adenoviridae, pubmed-meshheading:10476213-Animals, pubmed-meshheading:10476213-COS Cells, pubmed-meshheading:10476213-Cell Membrane, pubmed-meshheading:10476213-Cystic Fibrosis, pubmed-meshheading:10476213-Epithelium, pubmed-meshheading:10476213-Flow Cytometry, pubmed-meshheading:10476213-Gene Expression, pubmed-meshheading:10476213-Gene Therapy, pubmed-meshheading:10476213-Gene Transfer Techniques, pubmed-meshheading:10476213-Genetic Vectors, pubmed-meshheading:10476213-Liposomes, pubmed-meshheading:10476213-Microscopy, Confocal, pubmed-meshheading:10476213-Microscopy, Electron, Scanning, pubmed-meshheading:10476213-Models, Biological, pubmed-meshheading:10476213-Mucus, pubmed-meshheading:10476213-Sheep, pubmed-meshheading:10476213-Sputum, pubmed-meshheading:10476213-Trachea, pubmed-meshheading:10476213-Treatment Failure, pubmed-meshheading:10476213-beta-Galactosidase
pubmed:year
1999
pubmed:articleTitle
The extra- and intracellular barriers to lipid and adenovirus-mediated pulmonary gene transfer in native sheep airway epithelium.
pubmed:affiliation
Ion Transport Unit, Imperial College, National Heart and Lung Institute, London, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't