PMID: 9557654Apr 29, 1998Paper

Scaffold attachment region-mediated enhancement of retroviral vector expression in primary T cells

Journal of Virology
M AgarwalI Plavec

Abstract

We have studied retroviral transgene expression in primary human lymphocytes. Our data demonstrate that transgene expression is high in activated primary CD4+ T cells but significantly decreased in mitotically quiescent cells. Incorporation of a DNA fragment from the scaffold attachment region (SAR) of the human beta interferon gene into the vector improved transgene expression, particularly in quiescent cells. The SAR element functioned in an orientation-dependent manner and enhanced expression of Moloney murine leukemia virus- and murine embryonic stem cell-based vectors. Clonal analysis of transduced T cells showed that the SAR sequence did not confer position-independent expression on a transgene but rather prevented the decrease of expression when cells became quiescent. The SAR sequence also enhanced transgene expression in T cells generated from retrovirally transduced CD34-enriched hematopoietic progenitor-stem cells in a SCID-hu thymus-liver mouse model. We have used the SAR-containing retroviral vector to express the RevM10 gene, a trans-dominant mutant of the human immunodeficiency virus type 1 (HIV-1) Rev gene. Compared to a standard retroviral vector, the SAR-containing vector was up to 2 orders of magnitude more e...Continue Reading

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Citations

Oct 31, 2000·Current Opinion in Hematology·M SadelainI Rivière
Feb 24, 2001·The Journal of Gene Medicine·P Y Lam, X O Breakefield
Dec 1, 2001·Expert Opinion on Biological Therapy·N DüzgünesM C Pedroso de Lima
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Aug 12, 2003·Biotechnology and Bioengineering·Christina ValkovaGeorgi Milchev
Jul 10, 2004·Human Gene Therapy·Laurence J N CooperPhilip D Greenberg
May 13, 2005·Biotechnology and Bioengineering·Pierre-Alain GirodNicolas Mermod
Mar 4, 2005·Molecular and Cellular Biology·Sandra GoetzeJürgen Bode
Jun 7, 2005·Expert Opinion on Biological Therapy·Luisa BarzonGiorgio Palù
Nov 18, 2016·Scientific Reports·Karim BenabdellahFrancisco Martin
Apr 12, 2001·Journal of Internal Medicine·D B Kohn
Jul 31, 2009·Journal of Dental Research·E L Scheller, P H Krebsbach
Jun 23, 2011·PloS One·Cheryl L SershenCraig J Benham
Jul 13, 2000·Human Gene Therapy·S Halene, D B Kohn
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Jan 19, 2002·Journal of Virology·Gudrun SchiednerStefan Kochanek
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Nov 25, 2000·Journal of Hematotherapy & Stem Cell Research·Y HanazonoC E Dunbar
Sep 10, 2008·Proceedings of the National Academy of Sciences of the United States of America·Patrick SternRichard O Hynes
Jan 30, 2014·Nucleic Acids Research·Santhosh Chakkaramakkil VerghesePeter Kurre
Jun 18, 1999·Annals of the New York Academy of Sciences·D W Emery, G Stamatoyannopoulos

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