Comparison of five retrovirus vectors containing the human IL-2 receptor gamma chain gene for their ability to restore T and B lymphocytes in the X-linked severe combined immunodeficiency mouse model

Molecular Therapy : the Journal of the American Society of Gene Therapy
G J Avilés MendozaD M Bodine

Abstract

X-linked severe combined immunodeficiency (XSCID) is caused by mutations in the IL-2 receptor gamma chain (IL2RG) gene, resulting in absent T lymphocytes and nonfunctional B lymphocytes. Recently T lymphocyte production and B lymphocyte function were restored in XSCID patients infused with autologous stem cells transduced with a retrovirus containing the human IL2RG cDNA. To optimize the expression of human IL2RG for future clinical trials, we compared five retroviral vectors expressing human IL2RG from different LTR enhancer-promoter elements in a mouse model. Northern and Southern blot analysis of hematopoietic tissues from repopulated mice revealed that the retroviral vector with the highest expression per copy number was MFG-S-hIL2RG, followed by MND-hIL2RG. All five vectors were capable of restoring lymphopoiesis in irradiated XSCID mice transplanted with transduced IL2RG-deficient hematopoietic stem cells. Transduction of IL2RG-deficient hematopoietic stem cells with all five vectors restored T lymphopoiesis in transplanted stem cell-deficient W/W(v) mouse recipients. However, only XSCID stem cells transduced with the MFG-S-hIL2RG vector generated B lymphocytes in W/W(v) mice. We conclude that the MFG-S-hIL2RG vector prov...Continue Reading

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Citations

May 21, 2011·Human Gene Therapy·Kathryn S LintermanStephanie M Hughes
Apr 6, 2006·Journal of Periodontology·Erica GemmellGregory J Seymour
Feb 4, 2014·International Journal of Hematology·Fabio Candotti
Jan 12, 2007·Periodontology 2000·Erica GemmellGregory J Seymour
Jan 27, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Christopher BaumDavid A Williams
May 16, 2006·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Teresa RodriguesPedro E Cruz
Apr 28, 2006·Nature·Niels-Bjarne WoodsInder M Verma
Jul 4, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Divya PunwaniJennifer M Puck
Feb 24, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stefania AmorosiClaudio Pignata

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