PMID: 8995665Feb 1, 1997Paper

High-efficiency transduction of human lymphoid progenitor cells and expression in differentiated T cells

Journal of Virology
D S AnI S Chen

Abstract

Gene therapy strategies for humans have been limited by low transduction efficiencies and poor expression of retroviral vectors in differentiated progeny cells carrying the transduced vector. Here we describe a strategy utilizing a cell surface reporter gene, murine thy-1.2, selectable by fluorescence-activated cell sorting (FACS), to achieve higher gene marking efficiencies. Human CD34-positive cells were transduced by a murine retroviral vector bearing the thy-1.2 marker and pseudotyped with vesicular stomatitis virus G protein, followed by FACS to enrich for CD34-positive cells that express Thy-1.2 on the cell surface. Gene marking and expression after differentiation into thymocytes were assessed in a SCID-hu Thy/Liv mouse model for human lymphoid progenitor cell gene therapy. We found that virtually all of the differentiated T-cell progeny were marked with vector sequences. It is of particular importance that reconstitution with the selected cells resulted in expression of Thy-1.2 in up to 71% of donor-derived thymocytes. It is of note that the donor-derived thymocytes that did not express Thy-1.2 still harbored vector thy-1.2 sequences, suggesting repression of transgene expression in some cells during progenitor cell dif...Continue Reading

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Citations

Feb 8, 2003·Human Gene Therapy·Kouki MorizonoMarc H Hedrick
Nov 19, 2004·The European Journal of Neuroscience·Maki KamadaHiromu Yawo
Feb 13, 2002·AIDS Patient Care and STDs·Mario R Mautino, Richard A Morgan
Oct 24, 2006·Nature Medicine·Michael W MelkusJ Victor Garcia
Jun 17, 2005·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Dessislava I DimitrovaRobert J Suhadolnik
Jan 14, 1999·British Journal of Haematology·M SanchezG Migliaccio
May 22, 2002·The Journal of Biological Chemistry·Baojie LiStephen P Goff
Apr 3, 2008·Microbiology and Immunology·Hiroko KitayamaYoshio Koyanagi
May 15, 2018·Frontiers in Immunology·Mayra A CarrilloScott G Kitchen

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