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Blood, 15 October 2003, Vol. 102, No. 8, pp. 2789-2797. Prepublished online as a Blood First Edition Paper on June 26, 2003; DOI 10.1182/blood-2002-05-1482. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-05-1482v1 102/8/2789    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Brenner, S. Articles by Malech, H. L. Search for Related Content PubMed PubMed Citation Articles by Brenner, S. Articles by Malech, H. L. Related Collections Hematopoiesis and Stem Cells Phagocytes Signal Transduction Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Concentrated RD114-pseudotyped MFGS-gp91phox vector achieves high levels of functional correction of the chronic granulomatous disease oxidase defect in NOD/SCID/2-microglobulin–/– repopulating mobilized human peripheral blood CD34+ cells Sebastian Brenner, Narda L. Whiting-Theobald, Gilda F. Linton, Kevin L. Holmes, Mindy Anderson-Cohen, Patrick F. Kelly, Elio F. Vanin, André M. Pilon, David M. Bodine, Mitchell E. Horwitz, and Harry L. Malech From the Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; Division of Experimental Hematology, Children's Hospital Medical Center, Cincinnati, OH; Division of Experimental Hematology, Department of Hematology/Oncology, St Jude Children's Research Hospital, Memphis, TN; Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD; and the Department of Pediatrics, University Clinic "Carl Gustav Carus," TU Dresden, Germany. In previous studies amphotropic MFGS-gp91phox (murine onco-retrovirus vector) was used in a clinical trial of X-linked chronic granulomatous disease (X-CGD) gene therapy to achieve transient correction of oxidase activity in 0.1% of neutrophils. We later showed that transduced CD34+ peripheral blood stem cells (CD34+ PBSCs) from this trial transplanted into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice resulted in correction of only 2.5% of human neutrophils. However, higher rates of transduction into stem cells are required. In the current study we demonstrate that the same vector (MFGS-gp91phox) pseudo-typed with RD114 envelope in a 4-day culture/transduction regimen results in a 7-fold increase in correction of NOD/SCID mouse repopulating X-CGD CD34+ PBSCs (14%-22% corrected human neutrophils; human cell engraftment 13%-67%). This increase may result from high expression of receptor for RD114 that we demonstrate on CD34+CD38– stem cells. Using RD114-MFGS encoding cyan fluorescent protein to allow similar studies of normal CD34+ PBSCs, we show that progressively higher levels of gene marking of human neutrophils (67%-77%) can be achieved by prolongation of culture/transduction to 6 days, but with lower rates of human cell engraftment. Our data demonstrate the highest reported level of functional correction of any inherited metabolic disorder in human cells in vivo with the NOD/SCID mouse system using onco-retrovirus vector. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Choi, T. L. Leto, L. Hunyady, K. J. Catt, Y. S. Bae, and S. G. Rhee Mechanism of Angiotensin II-induced Superoxide Production in Cells Reconstituted with Angiotensin Type 1 Receptor and the Components of NADPH Oxidase J. Biol. Chem., January 4, 2008; 283(1): 255 - 267. [Abstract] [Full Text] [PDF] S. Brenner, M. F. Ryser, N. L. Whiting-Theobald, M. Gentsch, G. F. Linton, and H. L. Malech The Late Dividing Population of {gamma}-Retroviral Vector Transduced Human Mobilized Peripheral Blood Progenitor Cells Contributes Most to Gene-Marked Cell Engraftment in Nonobese Diabetic/Severe Combined Immunodeficient Mice Stem Cells, July 1, 2007; 25(7): 1807 - 1813. [Abstract] [Full Text] [PDF] T. Kawai, U. Choi, L. Cardwell, S. S. DeRavin, N. Naumann, N. L. Whiting-Theobald, G. F. Linton, J. Moon, P. M. Murphy, and H. L. Malech WHIM syndrome myelokathexis reproduced in the NOD/SCID mouse xenotransplant model engrafted with healthy human stem cells transduced with C-terminus-truncated CXCR4 Blood, January 1, 2007; 109(1): 78 - 84. [Abstract] [Full Text] [PDF] R. M. Taylor, D. Baniulis, J. B. Burritt, J. M. Gripentrog, C. I. Lord, M. H. Riesselman, W. S. Maaty, B. P. Bothner, T. E. Angel, E. A. Dratz, et al. Analysis of Human Phagocyte Flavocytochrome b558 by Mass Spectrometry J. Biol. Chem., December 1, 2006; 281(48): 37045 - 37056. [Abstract] [Full Text] [PDF] M. L. Lucas, N. E. Seidel, C. D. Porada, J. G. Quigley, S. M. Anderson, H. L. Malech, J. L. Abkowitz, E. D. Zanjani, and D. M. Bodine Improved transduction of human sheep repopulating cells by retrovirus vectors pseudotyped with feline leukemia virus type C or RD114 envelopes Blood, July 1, 2005; 106(1): 51 - 58. [Abstract] [Full Text] [PDF] T. Ueda, S. Brenner, H. L. Malech, S. M. Langemeijer, S. Perl, M. Kirby, O. A. Phang, A. E. Krouse, R. E. Donahue, E. M. Kang, et al. Cloning and Functional Analysis of the Rhesus Macaque ABCG2 Gene: FORCED EXPRESSION CONFERS AN SP PHENOTYPE AMONG HEMATOPOIETIC STEM CELL PROGENY IN VIVO J. Biol. Chem., January 14, 2005; 280(2): 991 - 998. [Abstract] [Full Text] [PDF] S. Brenner, N. Whiting-Theobald, T. Kawai, G. F. Linton, A. G. Rudikoff, U. Choi, M. F. Ryser, P. M. Murphy, J. M.G. Sechler, and H. L. Malech CXCR4-Transgene Expression Significantly Improves Marrow Engraftment of Cultured Hematopoietic Stem Cells Stem Cells, December 1, 2004; 22(7): 1128 - 1133. [Abstract] [Full Text] [PDF] O. S. Kustikova, A. Wahlers, K. Kuhlcke, B. Stahle, A. R. Zander, C. Baum, and B. Fehse Dose finding with retroviral vectors: correlation of retroviral vector copy numbers in single cells with gene transfer efficiency in a cell population Blood, December 1, 2003; 102(12): 3934 - 3937. [Abstract] [Full Text] [PDF]

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