Linked Life Data

9874264

Source:http://linkedlifedata.com/resource/pubmed/id/9874264

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
1999-8-26
pubmed:abstractText
Effective adenoviral gene therapy requires efficient viral vector entry into epithelial cells. Injured airway epithelia display enhanced gene transfer, reflecting in part increased vector access to protected cell populations and/or protected basolateral membranes. We tested whether adenoviral gene transfer is enhanced by modification of the epithelial barrier in mouse nasal airways with a nonionic detergent (polidocanol, PDOC). In C57BL/6 mice, 1.6 x 10(9) PFU of Ad5CMV LacZ (AdLacZ) instilled into the right nostril produced negligible gene transfer to the nasal epithelium 2 days after dosing, but significant, dose-dependent increases in gene transfer were achieved by pretreatment with PDOC. Permeation of the electron-dense tracer lanthanum into the intercellular junctions of PDOC (0.1%)-treated murine nasal epithelium, but not into intercellular junctions of vehicle controls, is consistent with PDOC-mediated increases in tight junctional permeability. In CF(-/-) mice, significant gene expression was not detectable after exposure to Ad5CBCFTR alone (1.4 x 10(9) PFU in 20 microl; AdCFTR), but PDOC pretreatment prior to AdCFTR instillation produced functional expression of CFTR (measured as deltaPD) 5 days after instillation. Because the development and testing of lung gene therapy will principally occur in children and adults with airway disease, AdLacZ gene transfer with and without PDOC pretreatment was examined in infected nasal airways. Gene expression was significantly reduced in infected as compared with uninfected airways. We conclude that the use of adjuvant surface-active and/or membrane-perturbing agents, synthetic or naturally derived, may provide a novel approach to enhancing the efficiency of adenoviral gene transfer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1043-0342
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2661-72
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Enhanced in vivo airway gene transfer via transient modification of host barrier properties with a surface-active agent.
pubmed:affiliation
Cystic Fibrosis Center, Department of Medicine, University of North Carolina at Chapel Hill, 27599, USA. parsonsd@wch.sa.gov.au
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't