Linked Life Data

17015408

Source:http://linkedlifedata.com/resource/pubmed/id/17015408

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2006-11-1
pubmed:abstractText
Sleeping Beauty (SB) transposon is a natural nonviral gene transfer system that can mediate long-term transgene expression. Its potential utility in treating organ transplantation-associated long-term complications has not yet been explored. In the present study we generated an improved SB transposon encoding the human gene indoleamine-2,3-dioxygenase (hIDO), an enzyme that possesses both T cell-suppressive and antioxidant properties and selectively delivered the SB transposon in combination with a hyperactive transposase plasmid to donor lung using the cationic polymer polyethylenimine (PEI) as transfection reagent. This nonviral gene therapeutic approach led to persistent and uniform transgene expression in the rat lung tissue without noticeable toxicity and inflammation. Importantly, IDO activity produced by hIDO transgene showed a remarkable therapeutic response, as evident by near normal pulmonary function (peak airway pressure and oxygenation), histological appearance, and reduced collagen content in lung allografts. In addition, we established a hIDO-overexpressing type II cell line using the SB-based gene transfer system and found that hIDO-overexpressing lung cells effectively inhibited transforming growth factor-beta-stimulated fibroblast proliferation in vitro. In summary, the SB-based gene therapy with hIDO represents a new strategy for treating lung transplantation-associated chronic complications, e.g., obliterative bronchiolitis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2384-6
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Sleeping Beauty-based gene therapy with indoleamine 2,3-dioxygenase inhibits lung allograft fibrosis.
pubmed:affiliation
Department of Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
pubmed:publicationType
Journal Article