16464640

Source:http://linkedlifedata.com/resource/pubmed/id/16464640

Download in:

Switch to

Custom View

Named Graph Language Inference

Statements in which the resource exists as a subject.
Predicate	Object
rdf:type	pubmed:Citation
lifeskim:mentions	umls-concept:C0004898, umls-concept:C0017262, umls-concept:C0019069, umls-concept:C0021289, umls-concept:C0026809, umls-concept:C0185117, umls-concept:C0424522, umls-concept:C0600401, umls-concept:C1366370, umls-concept:C1704822, umls-concept:C1947976, umls-concept:C2732002, umls-concept:C2911684
pubmed:issue	5
pubmed:dateCreated	2006-4-28
pubmed:abstractText	Hemophilia A, deficiency of coagulation factor VIII (FVIII), is an attractive candidate for gene therapy as expression of modest amounts of FVIII can provide therapeutic benefit. Most gene transfer approaches for hemophilia have focused on the liver, as this is the major source of endogenous FVIII; however, increasing evidence suggests that endothelial cells are capable of synthesis and release of FVIII. Here the Sleeping Beauty (SB) transposon is employed to target long-term expression of the human B-domain-depleted FVIII gene (approved gene symbol F8) within lung endothelia of hemophilic mice. As the formation of inhibitory antibodies to FVIII has been a significant impediment toward achieving therapeutic plasma levels after gene or protein therapy, we chose to perform gene transfer in neonatal mice, which are more likely to be immune tolerant. Using this approach, low therapeutic levels of FVIII ( approximately 10%), as well as phenotypic correction of the bleeding disorder, were achieved in all animals that received the FVIII transposon and functional transposase throughout the duration of the study (24 weeks). Rechallenge of these animals with additional gene transfer did not result in significant increases in FVIII levels, due mainly to increases in inhibitory antibodies. These studies demonstrate the feasibility of using endothelial-targeted SB transposons for the treatment of hemophilia A.
pubmed:language	eng
pubmed:journal	http://linkedlifedata.com/resource/pubmed/journal/100890581
pubmed:citationSubset	IM
pubmed:chemical	http://linkedlifedata.com/resource/pubmed/chemical/Factor VIII, http://linkedlifedata.com/resource/pubmed/chemical/Transposases, http://linkedlifedata.com/resource/pubmed/chemical/sleeping beauty transposase, human
pubmed:status	MEDLINE
pubmed:month	May
pubmed:issn	1525-0016
pubmed:author	pubmed-author:FletcherBradley SBS, pubmed-author:JosKK, pubmed-author:MahCathrynC
pubmed:issnType	Print
pubmed:volume	13
pubmed:owner	NLM
pubmed:authorsComplete	Y
pubmed:pagination	1006-15
pubmed:dateRevised	2006-11-15
pubmed:meshHeading	pubmed-meshheading:16464640-Animals, pubmed-meshheading:16464640-Animals, Newborn, pubmed-meshheading:16464640-Blood Coagulation, pubmed-meshheading:16464640-Cell Line, pubmed-meshheading:16464640-Endothelium, Vascular, pubmed-meshheading:16464640-Factor VIII, pubmed-meshheading:16464640-Feasibility Studies, pubmed-meshheading:16464640-Gene Expression, pubmed-meshheading:16464640-Gene Therapy, pubmed-meshheading:16464640-Gene Transfer Techniques, pubmed-meshheading:16464640-Hemophilia A, pubmed-meshheading:16464640-Humans, pubmed-meshheading:16464640-Immune Tolerance, pubmed-meshheading:16464640-Mice, pubmed-meshheading:16464640-Mice, Inbred C57BL, pubmed-meshheading:16464640-Mice, Knockout, pubmed-meshheading:16464640-Phenotype, pubmed-meshheading:16464640-Transposases
pubmed:year	2006
pubmed:articleTitle	Sustained FVIII expression and phenotypic correction of hemophilia A in neonatal mice using an endothelial-targeted sleeping beauty transposon.
pubmed:affiliation	Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, FL 32610, USA.
pubmed:publicationType	Journal Article, Comparative Study, Research Support, Non-U.S. Gov't