Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2005-11-1
pubmed:abstractText
Transient local overexpression of genes that promote lung defense or repair may help to protect or promote alveolar development in premature neonates. We showed that the use of adenoviral vectors in neonates was limited by the induction of lung growth disorders. In the present work we compare the efficiency of gene transfer to the neonatal lung by three adeno-associated viral vectors: rAAV1, rAAV2, and rAAV5. Transduction efficiency was first measured in vitro, by infecting A549 immortalized human lung epithelial cells, and primary epithelial and mesenchymal cells isolated from human fetal lung. AAV vectors yielded similar low levels of luciferase gene expression in the different cell types. In vivo transduction efficiency was evaluated in newborn rats, with AAV-LacZ vectors being intratracheally instilled at 3 days of age. Both rAAV5 and rAAV1, but not rAAV2, induced significant lung beta-galactosidase expression, which persisted on day 35. Highest beta- galactosidase levels were measured with rAAV5, but remained far lower than those obtained with adenoviral vectors. A transient increase in alveolar macrophages was observed on day 6, but not on day 8, after rAAV5-LacZ instillation. Morphometric evaluation of lung structures was performed on day 21, and showed no altered lung growth. We conclude that rAAV1 or rAAV5 was more efficient at mediating gene transfer in the neonatal lung than was rAAV2, without adversely affecting lung development. However, in vivo transgene expression was relatively low, and needs to be improved for future therapeutic use of these adeno-associated vectors.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1043-0342
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1298-306
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Comparative efficacy of intratracheal adeno-associated virus administration to newborn rats.
pubmed:affiliation
INSERM U651, Faculté de Médecine, 94010 Créteil, France.
pubmed:publicationType
Journal Article, Comparative Study