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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2008-5-12
pubmed:abstractText
A major limitation of current lentiviral vectors (LVs) is their inability to govern efficient gene transfer into quiescent cells, such as human CD34+ cells that reside in the G0 phase of the cell cycle and that are highly enriched in hematopoietic stem cells. This hampers their application for gene therapy of hematopoietic cells. We describe here novel LVs that overcome this restriction by displaying early-acting cytokines on their surface. Display of thrombopoietin, stem cell factor or both cytokines on LV surface allows high transfer into quiescent cord blood CD34+ cells. Moreover, these surface-engineered LVs preferentially transduce and promote survival of resting CD34+ cells rather than cycling cells. These novel LVs allow superior gene transfer in the most immature CD34+ cells compared to conventional LVs, even in the presence of recombinant cytokines. This is demonstrated by their capacity to promote selective transduction in long-term culture initiating cell colonies (LTC-ICs) and of long-term non-obese diabetic/severe combined immunodeficient (NOD/SCID) repopulating cells (SRCs). Here we describe the production of these "early acting cytokine" displaying vectors and the methodology to confirm the capacity of these vectors to promote selective transduction of HSCs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1064-3745
pubmed:author
pubmed:issnType
Print
pubmed:volume
434
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
99-112
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Production of lentiviruses displaying ''early-acting'' cytokines for selective gene transfer into hematopoietic stem cells.
pubmed:affiliation
Ecole Normale Supérieure de Lyon, BioSciences Lyon-Gerland, Lyon, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't