Linked Life Data

17090654

Source:http://linkedlifedata.com/resource/pubmed/id/17090654

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-2-7
pubmed:abstractText
The safety and efficacy of peripheral venous administration of a self-complementary adeno-associated viral vector encoding the human FIX gene (scAAV-LP1-hFIXco) was evaluated in nonhuman primates for gene therapy of hemophilia B. Peripheral vein infusion of 1x10(12) vg/kg scAAV-LP1-hFIXco pseudotyped with serotype 8 capsid, in 3 macaques, resulted in stable therapeutic expression (more than 9 months) of human FIX (hFIX) at levels (1.1+/-0.5 microg/mL, or 22% of normal) that were comparable to those achieved after direct delivery of the same vector dose into the portal circulation (1.3+/-0.3 microg/mL, or 26% of normal). Importantly, the pattern of vector biodistribution after systemic and portal vein administration of scAAV-LP1-hFIXco was almost identical. Additionally, comparable levels of gene transfer were achieved in macaques with preexisting immunity to AAV8 following peripheral vein administration of 1x10(12) vg/kg AAV5-pseudotyped scAAV-LP1-hFIXco. This confirms that alternative serotypes can circumvent preexisting naturally acquired immunity to AAV. Thus, peripheral venous administration of AAV5 and AAV8 vectors is safe and as effective at transducing the liver in nonhuman primates as direct vector administration into the portal circulation. These results should make vector administration to patients, especially those with a severe bleeding diathesis, significantly easier and safer.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/17090654-10666273, http://linkedlifedata.com/resource/pubmed/commentcorrection/17090654-10694794, http://linkedlifedata.com/resource/pubmed/commentcorrection/17090654-10933950, http://linkedlifedata.com/resource/pubmed/commentcorrection/17090654-11222368, http://linkedlifedata.com/resource/pubmed/commentcorrection/17090654-11389010, http://linkedlifedata.com/resource/pubmed/commentcorrection/17090654-12176886, http://linkedlifedata.com/resource/pubmed/commentcorrection/17090654-12192090, http://linkedlifedata.com/resource/pubmed/commentcorrection/17090654-12239326, http://linkedlifedata.com/resource/pubmed/commentcorrection/17090654-12727926, http://linkedlifedata.com/resource/pubmed/commentcorrection/17090654-12791653, http://linkedlifedata.com/resource/pubmed/commentcorrection/17090654-14625564, http://linkedlifedata.com/resource/pubmed/commentcorrection/17090654-14625565, http://linkedlifedata.com/resource/pubmed/commentcorrection/17090654-14990730, http://linkedlifedata.com/resource/pubmed/commentcorrection/17090654-15163731, http://linkedlifedata.com/resource/pubmed/commentcorrection/17090654-15381358, http://linkedlifedata.com/resource/pubmed/commentcorrection/17090654-15596817, http://linkedlifedata.com/resource/pubmed/commentcorrection/17090654-15922958, http://linkedlifedata.com/resource/pubmed/commentcorrection/17090654-16322469, http://linkedlifedata.com/resource/pubmed/commentcorrection/17090654-16474400, http://linkedlifedata.com/resource/pubmed/commentcorrection/17090654-7495077
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
109
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1414-21
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Safe and efficient transduction of the liver after peripheral vein infusion of self-complementary AAV vector results in stable therapeutic expression of human FIX in nonhuman primates.
pubmed:affiliation
Department of Haemotology, University College London, UK, and Department of Surgery, St Jude Children's Research Hospital, Memphis, TN, USA. a.nathwani@ucl.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural