Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1996-11-22
pubmed:abstractText
The efficiency of adenovirus-mediated gene transfer to airway epithelia will be an important factor in determining whether recombinant adenoviruses can be developed as vectors for transferring cystic fibrosis transmembrane conductance regulator (CFTR) cDNA to patients with cystic fibrosis. Current understanding of the biology of CF lung disease suggests that vectors should express transgene in mature, ciliated airway epithelia. We evaluated the efficiency of adenovirus-mediated gene transfer to primary cultures of normal and CF human airway epithelia. Our studies showed that the airway cells developed from an undifferentiated epithelium with markers characteristic of basal cells and a surface covered by short microvilli 3 days after seeding to a mature epithelium whose apical surface was covered with cilia by 10 to 14 days. The ability of adenovirus vectors to express a reporter gene and to correct defective cyclic AMP-stimulated Cl- transport in CF epithelia was correlated inversely with the state of differentiation. However, the inefficiency of adenovirus-mediated gene transfer could be partially corrected when the contact time between vector and epithelium was prolonged. After prolonged contact, we observed complete correction of the CF Cl- transport defect in differentiated CF airway epithelia in culture and of the Cl- transport defect in the nasal epithelia of mice homozygous for the deltaF508 mutation. The fact that gene transfer to airway epithelia required prolonged incubation with vector contrasts with the rapid infection observed in cell models such as 293 and HeLa cells, which are commonly used to study adenovirus infection. Gene transfer observed after prolonged incubation may result from mechanisms different from those that mediate infection of 293 cells. These observations suggest that interventions that either increase the contact time or alter the epithelium or the vector may be required to facilitate gene transfer to ciliated respiratory epithelia.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-1284642, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-1465433, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-1540382, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-1616056, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-1651662, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-1763032, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-2196380, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-2407138, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-2474472, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-3102226, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-3973985, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-4301496, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-7511023, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-7514446, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-7519884, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-7523420, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-7523956, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-7527271, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-7536280, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-7537540, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-7544439, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-7545239, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-7560099, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-7584081, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-7685651, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-7691187, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-7691415, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-7703286, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-7707507, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-7900815, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-7973726, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-8183921, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-8221887, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-8297578, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-8380066, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-8455602, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-8573621, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-8617884, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-8642632, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-8867859, http://linkedlifedata.com/resource/pubmed/commentcorrection/8794344-921054
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-538X
pubmed:author
pubmed:issnType
Print
pubmed:volume
70
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6994-7003
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Adenovirus-mediated gene transfer to ciliated airway epithelia requires prolonged incubation time.
pubmed:affiliation
Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City 52242, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't