Restriction of transgene expression to the B-lymphoid progeny of human lentivirally transduced CD34+ cells

Molecular Therapy : the Journal of the American Society of Gene Therapy
Thomas MoreauC Tonnelle

Abstract

Development of gene transfer strategies will necessitate improved efficiency and control of transduction and transgene expression. We here provide evidence that targeting expression of the GFP reporter gene to the B-lymphoid progeny of genetically modified human hematopoietic progenitor cells can be achieved through the insertion of regulatory sequences from the human CD19 gene promoter into a lentiviral vector. Based on a bioinformatics approach, three human CD19-derived sequences were designed and inserted into a self-inactivated lentiviral vector backbone upstream of the GFP gene: S.CD19 (230 bp), M.CD19 (464 bp), and L.CD19 (1274 bp). These new lentiviral vectors efficiently transduced cord blood CD34(+) cells. The M.CD19 and especially L.CD19 sequences preferentially targeted GFP expression to in vitro and in vivo differentiated CD19(+) progeny; moreover, transgene expression was detected from the CD34(+) pro/pre-B cell to the mature peripheral IgM(+) B cell stage. In contrast, GFP expression was weak or absent in primary T-lymphoid and uncommitted progenitor cells or in erythroid, natural killer, or myeloid differentiated cells. Such B-lineage-specific lentiviral vectors may be useful for correcting inherited disorders th...Continue Reading

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Citations

Jul 2, 2008·Human Gene Therapy·Leslie ZieglerPin Wang
Dec 9, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Blythe D SatherDavid J Rawlings
Jun 14, 2012·Human Gene Therapy·Christine RivatAdrian J Thrasher
Jul 28, 2009·Human Gene Therapy·Miguel G ToscanoFrancisco Martín
Aug 26, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Cecilia FrechaEls Verhoeyen
Oct 16, 2007·Blood·Marilyne DijonCécile Tonnelle
Jan 21, 2010·Immunopharmacology and Immunotoxicology·Steven FroelichPin Wang
May 16, 2014·Expert Opinion on Biological Therapy·Fabien TouzotMarina Cavazzana
Apr 5, 2011·European Journal of Cell Biology·Romana I FriedrichThomas Brocker
Apr 10, 2013·Gene·Sayandip Mukherjee, Adrian J Thrasher
Jun 13, 2017·Expert Opinion on Biological Therapy·Antonela S AsadMarianela Candolfi
Mar 20, 2012·Cellular & Molecular Immunology·Adam C DrakeJianzhu Chen
Jun 6, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Melanie Werner-KleinThomas Brocker

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