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Titolo:
Hybrid HIV/MSCV LTR enhances transgene expression of lentiviral vectors inhuman CD34(+) hematopoietic cells
Autore:
Choi, JK; Hoang, N; Vilardi, AM; Conrad, P; Emerson, SG; Gewirtz, AM;
Indirizzi:
Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA Univ Penn Philadelphia PA USA 19104 & Lab Med, Philadelphia, PA 19104 USA Univ Penn, Dept Med, Philadelphia, PA 19104 USA Univ Penn Philadelphia PAUSA 19104 Dept Med, Philadelphia, PA 19104 USA Childrens Hosp, Dept Pediat, Philadelphia, PA 19104 USA Childrens Hosp Philadelphia PA USA 19104 diat, Philadelphia, PA 19104 USA
Titolo Testata:
STEM CELLS
fascicolo: 3, volume: 19, anno: 2001,
pagine: 236 - 246
SICI:
1066-5099(2001)19:3<236:HHLETE>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
IMMUNODEFICIENCY-VIRUS TYPE-1; MURINE LEUKEMIA-VIRUS; HIV-1 TAT PROTEIN; GENE-TRANSFER; IN-VIVO; STABLE TRANSDUCTION; RETROVIRAL VECTORS; NONDIVIDING CELLS; STEM-CELLS; EFFICIENT;
Keywords:
lentiviral vector; MSCV-based vector; human CD34(+) cells; hybrid LTR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Choi, JK Univ Penn, Dept Pathol & Lab Med, 413A SCL,422 Curie Blvd, Philadelphia, PA 19104 USA Univ Penn 413A SCL,422 Curie Blvd Philadelphia PA USA 19104 4 USA
Citazione:
J.K. Choi et al., "Hybrid HIV/MSCV LTR enhances transgene expression of lentiviral vectors inhuman CD34(+) hematopoietic cells", STEM CELLS, 19(3), 2001, pp. 236-246

Abstract

HIV-based lentiviral vectors can transduce nondividing cells, an importantadvantage over murine leukemia virus (MLV)-based vectors when transducing slowly dividing hematopoietic stem cells. However, we find that in human CD34(+) hematopoietic cells, the HIV-based vectors with an internal cytomegalovirus (CMV) promoter express transgenes 100- to 1,000-fold less than the MLV-based retroviral vector murine stem cell virus (MSCV), To increase the expression of the integrated lentivirus, we replaced CMV promoter with that of the Rous sarcoma virus or MSCV and obtained a modest augmentation in expression. A more dramatic effect was seen when the CMV enhancer/promoter wasremoved and the HIV long-terminal repeat (LTR) was replaced by a novel HIV/MSCV hybrid LTR, This vector retains the ability to transduce nondividing cells hut now expresses its transgene (enhanced green fluorescent protein) 10- to 100-fold greater than the original HIV-based vector. When compared under identical conditions, the HIV vector with the hybrid I,TR transduced ahigher percentage of CD34(+) cells than the MSCV-based retroviral vector (19.4% versus 2.4%). The number of transduced cells and level of transgene expression remain constant over 5-8 weeks as determined by longterm culture-initiating cells, fluoresence-activated cell sorting, and nonobese diabetic/severe combined immunodeficiency repopulation assay.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/08/20 alle ore 15:54:51