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Titolo:
Hematopoietic stem cell gene therapy: towards clinically significant gene transfer efficiency
Autore:
Heim, DA; Dunbar, CE;
Indirizzi:
NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA NHLBI Bethesda MD USA 20892 , Hematol Branch, NIH, Bethesda, MD 20892 USA
Titolo Testata:
IMMUNOLOGICAL REVIEWS
, volume: 178, anno: 2000,
pagine: 29 - 38
SICI:
0105-2896(200012)178:<29:HSCGTT>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
COLONY-STIMULATING FACTOR; AUTOLOGOUS BONE-MARROW; PERIPHERAL-BLOOD LYMPHOCYTES; LONG-TERM EXPRESSION; GREEN FLUORESCENT PROTEIN; HUMAN ADENOSINE-DEAMINASE; APE LEUKEMIA-VIRUS; EX-VIVO EXPANSION; IN-VIVO; PROGENITOR CELLS;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
88
Recensione:
Indirizzi per estratti:
Indirizzo: Dunbar, CE Bldg 10 Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USABldg 10 Room 7C103,9000 Rockville Pike Bethesda MD USA 20892 A
Citazione:
D.A. Heim e C.E. Dunbar, "Hematopoietic stem cell gene therapy: towards clinically significant gene transfer efficiency", IMMUNOL REV, 178, 2000, pp. 29-38

Abstract

Early clinical gene therapy and gene marking trials using retroviral vectors to transduce hematopoietic stem cells (HSC) revealed mio major shortcomings of this new treatment modality. One nas insufficient expression or evensilencing of the integrated vector sequences, and the second was the low gene transfer efficiency achieved to in vivo repopulating cells. It became clear that neither rodent models nor human in vitro surrogate assays for stem cells were predictive of in rim transgene levels in human target cells. Using the rhesus monkey model we have focused on improving gene transfer efficiency into HSC. Immune rejection of transduced cells has been shown to occur in mature peripheral target cells such as lymphocytes or myocytes. Our studies and those from other investigators suggest that transgenes introduced via HSC induces immunologic tolerance towards the foreign product. In vivo priming of target cells, i.e. mobilization of HSC into the circulation with granulocyte colony stimulating factor and stem cell factor as well as optimization of the in vitro transduction conditions, now allow a stable in vivo gene transfer efficiency of up to 10-15% in both lymphoid and myeloid circulating cells in non-human primates, levels that would be adequate for many clinical applications.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 11:34:32