Source:http://linkedlifedata.com/resource/pubmed/id/17164778
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2006-12-13
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pubmed:abstractText |
Gene therapy for human immunodeficiency virus (HIV)-1 may be performed by introducing into hematopoietic stem cells genes that inhibit replication of HIV-1 using lentiviral vectors. However, production of lentiviral vectors derived from HIV-1 may be inhibited by the gene being carried to inhibit HIV-1 and these vectors could be mobilized by wild-type HIV-1 infecting transduced cells. This study investigates these problems for the delivery of a dominant-negative rev gene humanized revM10 (huM10) by a lentiviral vector. Although most packaging plasmids suffered inhibition of expression of HIV-1 virion proteins by vectors expressing huM10, the packaging plasmids that expressed the highest levels of HIV-1 virion proteins produced vectors at titers that would be sufficient for clinical applications. The vectors carrying huM10 were used to transduce primary human CD34(+) hematopoietic progenitor cells and yielded high-level transduction without toxicity and conferred potent inhibition of HIV-1. The use of lentiviral vectors with deletion of the enhancers and promoter from the LTR (self-inactivating (SIN) vectors) decreased the frequency of vector mobilization by wild-type HIV-1; SIN vectors carrying huM10 were not mobilized detectably. These studies indicate that lentiviral vectors can be made effective for use in gene therapy for HIV-1.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1525-0024
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
15
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
76-85
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pubmed:meshHeading |
pubmed-meshheading:17164778-Antigens, CD34,
pubmed-meshheading:17164778-Cell Line,
pubmed-meshheading:17164778-Gene Products, rev,
pubmed-meshheading:17164778-Genetic Vectors,
pubmed-meshheading:17164778-HIV-1,
pubmed-meshheading:17164778-Hematopoietic Stem Cells,
pubmed-meshheading:17164778-Humans,
pubmed-meshheading:17164778-Lentivirus,
pubmed-meshheading:17164778-Plasmids,
pubmed-meshheading:17164778-Transgenes,
pubmed-meshheading:17164778-Virus Replication
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pubmed:year |
2007
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pubmed:articleTitle |
Lentiviral vector transduction of a dominant-negative Rev gene into human CD34+ hematopoietic progenitor cells potently inhibits human immunodeficiency virus-1 replication.
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pubmed:affiliation |
Division of Research Immunology/Bone Marrow Transplantation, The Saban Research Institute of Childrens Hospital Los angeles, Los Angeles, California, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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