Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
10
|
| pubmed:dateCreated |
1998-10-28
|
| pubmed:abstractText |
One of the main impediments to effective gene therapy of blood disorders is the resistance of human hematopoietic stem cells to stable genetic modification. We show here that a small minority of retrovirally transduced stem cells can be selectively enriched in vivo, which might be a way to circumvent this obstacle. We constructed two retroviral vectors containing an antifolate-resistant dihydrofolate reductase cDNA transcriptionally linked to a reporter gene. Mice were transplanted with transduced bone marrow cells and then treated with an antifolate-based regimen that kills unmodified stem cells. Drug treatment significantly increased the percentage of vector-expressing peripheral blood erythrocytes, platelets, granulocytes, and T and B lymphocytes. Secondary transplant experiments demonstrated that selection occurred at the level of hematopoietic stem cells. This system for in vivo stem-cell selection provides a means to increase the number of genetically modified cells after transplant, and may circumvent an substantial obstacle to successful gene therapy for human blood diseases.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Folic Acid Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Tetrahydrofolate Dehydrogenase,
http://linkedlifedata.com/resource/pubmed/chemical/Thioinosine,
http://linkedlifedata.com/resource/pubmed/chemical/Thionucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Trimetrexate,
http://linkedlifedata.com/resource/pubmed/chemical/nitrobenzylthioinosine...
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
1078-8956
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
4
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1136-43
|
| pubmed:dateRevised |
2009-11-19
|
| pubmed:meshHeading |
pubmed-meshheading:9771746-Animals,
pubmed-meshheading:9771746-Blood Cells,
pubmed-meshheading:9771746-Drug Resistance,
pubmed-meshheading:9771746-Female,
pubmed-meshheading:9771746-Folic Acid Antagonists,
pubmed-meshheading:9771746-Gene Therapy,
pubmed-meshheading:9771746-Genes, Reporter,
pubmed-meshheading:9771746-Genetic Vectors,
pubmed-meshheading:9771746-Hematopoietic Stem Cell Transplantation,
pubmed-meshheading:9771746-Mice,
pubmed-meshheading:9771746-Mice, Inbred C57BL,
pubmed-meshheading:9771746-Retroviridae,
pubmed-meshheading:9771746-Selection, Genetic,
pubmed-meshheading:9771746-Tetrahydrofolate Dehydrogenase,
pubmed-meshheading:9771746-Thioinosine,
pubmed-meshheading:9771746-Thionucleotides,
pubmed-meshheading:9771746-Transformation, Genetic,
pubmed-meshheading:9771746-Trimetrexate
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
In vivo selection of retrovirally transduced hematopoietic stem cells.
|
| pubmed:affiliation |
Department of Hematology and Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|