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Titolo:
In vivo persistence of retrovirally transduced murine long-term repopulating cells is not limited by expression of foreign gene products in the fullyor minimally myeloablated setting
Autore:
Kang, E; Giri, N; Wu, T; Sellers, S; Kirby, M; Hanazono, Y; Tisdale, J; Dunbar, CE;
Indirizzi:
NHLBI, NIH, Hematol Branch, Mol Hematopoiesis Sect, Bethesda, MD 20892 USANHLBI Bethesda MD USA 20892 ol Hematopoiesis Sect, Bethesda, MD 20892 USA NIDDKD, Mol Clin Hematol Branch, Bethesda, MD 20892 USA NIDDKD Bethesda MD USA 20892 Clin Hematol Branch, Bethesda, MD 20892 USA Jichi Med Sch, Ctr Mol Med, Div Genet Therapeut, Tochigi, Japan Jichi Med Sch Tochigi Japan ol Med, Div Genet Therapeut, Tochigi, Japan
Titolo Testata:
HUMAN GENE THERAPY
fascicolo: 13, volume: 12, anno: 2001,
pagine: 1663 - 1672
SICI:
1043-0342(200109)12:13<1663:IVPORT>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
HEMATOPOIETIC STEM-CELLS; CHRONIC GRANULOMATOUS-DISEASE; GREEN FLUORESCENT PROTEIN; BONE-MARROW CELLS; IN-VIVO; PERIPHERAL-BLOOD; PROGENITOR CELLS; GLUCOCEREBROSIDASE GENE; NONHUMAN-PRIMATES; IMMUNE-RESPONSES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Dunbar, CE NHLBI, NIH, Hematol Branch, Mol Hematopoiesis Sect, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA NHLBI Bldg 10,Room 7C103,9000 Rockville Pike Bethesda MD USA 20892
Citazione:
E. Kang et al., "In vivo persistence of retrovirally transduced murine long-term repopulating cells is not limited by expression of foreign gene products in the fullyor minimally myeloablated setting", HUM GENE TH, 12(13), 2001, pp. 1663-1672

Abstract

Many nonmalignant hematologic disorders could potentially be treated by genetic correction of as few as 5-10% of target lineage cells. However, immune system clearance of cells expressing gene products perceived as foreign could be limiting. There is evidence that tolerance to foreign proteins can result when myeloablative conditioning is used, but this limits the overallapplicability of such techniques. Therefore, we sought to evaluate the engraftment of hematopoietic stem cells carrying a foreign transgene after low-dose irradiation by comparing in vivo survival of murine long-term repopulating cells (LTRC) transduced with either a retroviral vector expressing the bacterial neomycin phosphotransferase gene (neo) or a vector containing neo gene sequences but modified to prevent protein expression (nonexpression). First, marrow cells from congenic donors were transduced with either vector and transplanted into recipients treated with standard dose irradiationof 800 rads. High-level engraftment and gene marking resulted, without differences in the marking levels or pattern of persistence of the cells between cells transduced with either vector. Low-dose irradiation at 100 rads was tested using higher cell doses. Marking levels as high as 10% overall were obtained, again with no differences between mice receiving cells transduced with the neo versus the nonexpression vectors. To investigate a potentially more immunogenic protein, marrow cells were transduced with a vector containing the green fluorescent protein (GFP) gene, and their persistence was studied in recipient mice receiving 100 rads. Stable GFP expression in 5-10% of circulating cells was observed long term. We conclude that even withvery low dose conditioning, engraftment by genetically modified LTRC cellsat clinically significant levels can be achieved without evidence for clearance of cells known to be expressing immunogenic proteins.

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Documento generato il 18/01/20 alle ore 02:14:47