Sustained transgene expression by human cord blood derived CD34+ cells transduced with simian immunodeficiency virus agmTYO1-based vectors carrying the human coagulation factor VIII gene in NOD/SCID mice

The Journal of Gene Medicine
J KikuchiY Sakata

Abstract

Gene therapy is being studied as the next generation therapy for hemophilia and several clinical trials have been carried out, albeit with limited success. To explore the possibility of utilizing autologous bone marrow transplantation of genetically modified hematopoietic stem cells for hemophilia gene therapy, we investigated the efficacy of genetically engineered CD34+ cell transplantation to NOD/SCID mice for expression of human factor VIII (hFVIII). CD34+ cells were transduced with a simian immunodeficiency virus agmTYO1 (SIV)-based lentiviral vector carrying the enhanced green fluorescent protein (eGFP) gene (SIVeGFP) or the hFVIII gene (SIVhFVIII). CD34+ cells transduced with SIV vectors were transplanted to NOD/SCID mice. Engraftment of transduced CD34+ cells and expression of transgenes were studied. We could efficiently transduce CD34+ cells using the SIVeGFP vector in a dose-dependent manner, reaching a maximum (99.6 +/- 0.1%) at MOI of 5 x 10(3) vector genome/cell. After transducing CD34+ cells with SIVhFVIII, hFVIII was produced (274.3 +/- 20.1 ng) from 10(6) CD34+ cells during 24 h in vitro incubation. Transplantation of SIVhFVIII-transduced CD34+ cells (5-10 x 10(5)) at a multiplicity of infection (MOI) of 50 vect...Continue Reading

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Citations

Oct 22, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Michel SadelainLeszek Lisowski
Jan 18, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Alex H Chang, Michel Sadelain
Sep 23, 2006·Expert Opinion on Biological Therapy·Shu Uin GanRoy Y Calne
Jun 11, 2005·Journal of Thrombosis and Haemostasis : JTH·C Hough, D Lillicrap
Jul 8, 2015·Journal of Thrombosis and Haemostasis : JTH·T OhmoriS Nishimura
Feb 20, 2015·Hematology·Christopher B Doering, H Trent Spencer
Jul 18, 2006·Nature Biotechnology·Alex H ChangMichel Sadelain
May 26, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Tsukasa OhmoriYoichi Sakata
May 1, 2020·Frontiers in Immunology·Seema R PatelChristopher B Doering

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