Lentivirus-mediated gene transfer in primary T cells is enhanced by a central DNA flap

Gene Therapy
V DardalhonN Taylor

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, but not with the parental lentiviral vector nor an MuLV vector. Transgene expression in the flap-containing lentiviral vector, under the control of either an internal cytomegalovirus or the elongation...Continue Reading

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Citations

Oct 11, 2003·Experimental Hematology·Richard K BurtCharles Link
Aug 26, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Cecilia FrechaEls Verhoeyen
Feb 17, 2007·Nature Reviews. Microbiology·Youichi Suzuki, Robert Craigie
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Oct 9, 2012·The Journal of Biological Chemistry·Stuart F J Le Grice
Feb 8, 2003·DNA and Cell Biology·Ricardo Quinonez, Richard E Sutton
Jun 3, 2009·Human Gene Therapy·T MaggM H Albert
Sep 17, 2010·Journal of Virology·Chunling HuEric M Poeschla
Sep 29, 2006·Journal of Virology·David J GarfinkelStephen H Hughes
Jul 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·V DardalhonN Taylor
Jan 21, 2010·Immunopharmacology and Immunotoxicology·Steven FroelichPin Wang
Jun 9, 2007·Expert Opinion on Biological Therapy·Sara BobisseAntonio Rosato
Feb 22, 2008·Veterinary Immunology and Immunopathology·Román A Barraza, Eric M Poeschla
Oct 27, 2004·Journal of Molecular Biology·Peter SommerSimon Wain-Hobson
Jan 15, 2009·The Journal of General Virology·Tatiana WiktorowiczAxel Rethwilm
Jan 1, 2013·Journal of Drug Delivery Science and Technology·N H KimO M Merkel
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Jan 1, 2015·F1000Research·Youjin Lee, Vijay Kuchroo
Jul 29, 2003·Gene Therapy·S OkanoK Sueishi
May 7, 2003·Gene Therapy·D J Gould, P Favorov

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