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Titolo:
Lentivirus-mediated gene transfer in primary T cells is enhanced by a central DNA flap
Autore:
Dardalhon, V; Herpers, B; Noraz, N; Pflumio, F; Guetard, D; Leveau, C; Dubart-Kupperschmitt, A; Charneau, P; Taylor, N;
Indirizzi:
Inst Mol Genet, UMR 5535, IFR 22, F-34293 Montpellier 5, France Inst Mol Genet Montpellier France 5 FR 22, F-34293 Montpellier 5, France Inst Pasteur, INSERM, U474, Matern Port Royal, F-75724 Paris, France Inst Pasteur Paris France F-75724 tern Port Royal, F-75724 Paris, France Inst Pasteur, Unite Oncol Virale, F-75724 Paris, France Inst Pasteur Paris France F-75724 te Oncol Virale, F-75724 Paris, France
Titolo Testata:
GENE THERAPY
fascicolo: 3, volume: 8, anno: 2001,
pagine: 190 - 198
SICI:
0969-7128(200102)8:3<190:LGTIPT>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-IMMUNODEFICIENCY-VIRUS; PERIPHERAL-BLOOD LYMPHOCYTES; HUMAN HEMATOPOIETIC-CELLS; MURINE LEUKEMIA-VIRUS; RETROVIRAL VECTORS; IN-VIVO; REVERSE TRANSCRIPTION; STABLE TRANSDUCTION; NONDIVIDING CELLS; HIV-1 INFECTION;
Keywords:
lentiviral vector; DNA flap; gene transfer; primary T cells;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Taylor, N Inst Mol Genet, UMR 5535, IFR 22, 1919 Route Mende, F-34293 Montpellier 5,France Inst Mol Genet 1919 Route Mende Montpellier France 5 r 5,France
Citazione:
V. Dardalhon et al., "Lentivirus-mediated gene transfer in primary T cells is enhanced by a central DNA flap", GENE THER, 8(3), 2001, pp. 190-198

Abstract

Retroviral vectors have become the primary tool for gene delivery into hematopoietic cells, including T lymphocytes. Lentiviral vectors offer an advantage over moloney murine leukemia virus (MuLV) vectors because of their ability to translocate across an intact nuclear membrane and integrate into the genome of nonproliferating cells. We have recently demonstrated that a central strand displacement event, controlled by the central polypurine tract (cPPT) and the central termination sequence (CTS), results in the formation of a central DNA flap which acts as a cis-determinant of HIV-1 genome nuclear import Here, we show that insertion of this DNA determinant in a classical lentiviral vector resulted in a significantly higher level of transduction in activated T cells (51 +/- 12.7% versus 15 +/- 1.4%). CD4(+) and CD8(+) T cells were transduced at equivalent levels. Importantly, freshly isolated T cells stimulated only during the 12-h transduction period could be efficiently transduced with this new flap-containing lentiviral vector, brit not with the parental lentiviral vector nor an MuLV vector. Transgene expression in the flap-containing lenfiviral vector under the control of either an internal cytomegalovirus or the elongation factor-1 alpha (EF1 alpha) promoter was significant and expression remained elevated in resting T cells. Thus, this system allows stable expression of transgenes in T lymphocytes following a short ex vivo transduction protocol.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 22:11:03