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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
18
|
| pubmed:dateCreated |
1998-2-25
|
| pubmed:abstractText |
Gene therapy is a promising treatment modality for acquired immunodeficiency syndrome (AIDS). Autologous transplantation with genetically altered pluripotent hematopoietic stem cells encoding anti-human immunodeficiency virus (HIV) genes could in theory completely and permanently reconstitute all blood lineages and immune functions with cells resistant to HIV. Recent studies showed that CD34+ stem cell can be mobilized in HIV-infected individuals after granulocyte colony-stimulating factor (G-CSF) administration without major side effects or increase of viral load. In this study, peripheral blood CD34+ cells of five HIV-infected individuals were mobilized with G-CSF and after leukapheresis and enrichment, subjected to retroviral transduction with genes encoding anti-HIV ribozyme-decoy fusion molecules. These cells were tested for the ability to give rise to progeny cells, for retroviral transduction efficiency, and for expression of the transgene. CD34+-derived macrophage-like cells were also challenged with HIV. Results showed that CD34+ cells from HIV-infected individuals gave rise to similar numbers of progeny colonies as cells from healthy donors. The transduction efficiency of these cells varied from 68.8 to 100% as assessed by DNA polymerase chain reaction (PCR) of the transgene in individual colonies. CD34+-derived macrophages expressed anti-HIV genes and displayed a substantial and sustained inhibition of HIV replication as compared to untransduced cells. Furthermore, we showed that after thawing, cryopreserved CD34+ cells from these individuals have survival, proliferation, and transduction parameters comparable to fresh cells. Thus, CD34+ cells from HIV-infected patients can be stored for further genetic manipulations with improved vectors or anti-HIV genes as they become available.
|
| pubmed:grant | |
| pubmed:commentsCorrections | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Dec
|
| pubmed:issn |
1043-0342
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
10
|
| pubmed:volume |
8
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
2229-38
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:9449376-Animals,
pubmed-meshheading:9449376-Antigens, CD34,
pubmed-meshheading:9449376-Cell Line,
pubmed-meshheading:9449376-Cell Transformation, Viral,
pubmed-meshheading:9449376-Gene Therapy,
pubmed-meshheading:9449376-Genetic Vectors,
pubmed-meshheading:9449376-Granulocyte Colony-Stimulating Factor,
pubmed-meshheading:9449376-HIV Infections,
pubmed-meshheading:9449376-HIV-1,
pubmed-meshheading:9449376-Hematopoietic Stem Cells,
pubmed-meshheading:9449376-Humans,
pubmed-meshheading:9449376-Leukapheresis,
pubmed-meshheading:9449376-Leukocyte Count,
pubmed-meshheading:9449376-Leukocytes, Mononuclear,
pubmed-meshheading:9449376-Macrophages,
pubmed-meshheading:9449376-Mice,
pubmed-meshheading:9449376-Moloney murine leukemia virus,
pubmed-meshheading:9449376-Monocytes,
pubmed-meshheading:9449376-RNA, Catalytic,
pubmed-meshheading:9449376-Tumor Cells, Cultured
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
Gene therapy targeting peripheral blood CD34+ hematopoietic stem cells of HIV-infected individuals.
|
| pubmed:affiliation |
Department of Medicine, University of California at San Diego, La Jolla 92093-0665, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|