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Blood, 1 November 2003, Vol. 102, No. 9, pp. 3108-3116. Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2002-11-3489. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-11-3489v1 102/9/3108    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 Strom, T. S. Articles by Nienhuis, A. W. Search for Related Content PubMed PubMed Citation Articles by Strom, T. S. Articles by Nienhuis, A. W. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Cytoskeleton Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Defects in T-cell–mediated immunity to influenza virus in murine Wiskott-Aldrich syndrome are corrected by oncoretroviral vector–mediated gene transfer into repopulating hematopoietic cells Ted S. Strom, Stephen J. Turner, Samita Andreansky, Haiyan Liu, Peter C. Doherty, Deo Kumar Srivastava, John M. Cunningham, and Arthur W. Nienhuis From the Division of Experimental Hematology, the Department of Hematology/Oncology, the Department of Immunology, and the Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN; and the Departments of Biochemistry and Pediatrics, University of Tennessee, Memphis. The Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by immune dysfunction, thrombocytopenia, and eczema. We used a murine model created by knockout of the WAS protein gene (WASP) to evaluate the potential of gene therapy for WAS. Lethally irradiated, male WASP— animals that received transplants of mixtures of wild type (WT) and WASP— bone marrow cells demonstrated enrichment of WT cells in the lymphoid and myeloid lineages with a progressive increase in the proportion of WT T-lymphoid and B-lymphoid cells. WASP— mice had a defective secondary T-cell response to influenza virus which was normalized in animals that received transplants of 35% or more WT cells. The WASP gene was inserted into WASP— bone marrow cells with a bicistronic oncoretroviral vector also encoding green fluorescent protein (GFP), followed by transplantation into irradiated male WASP— recipients. There was a selective advantage for gene-corrected cells in multiple lineages. Animals with higher proportions of GFP+ T cells showed normalization of their lymphocyte counts. Gene-corrected, blood T cells exhibited full and partial correction, respectively, of their defective proliferative and cytokine secretory responses to in vitro T-cell–receptor stimulation. The defective secondary T-cell response to influenza virus was also improved in gene-corrected animals. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Bosticardo, F. Marangoni, A. Aiuti, A. Villa, and M. Grazia Roncarolo Recent advances in understanding the pathophysiology of Wiskott-Aldrich syndrome Blood, June 18, 2009; 113(25): 6288 - 6295. [Abstract] [Full Text] [PDF] A. Konno, M. Kirby, S. A. Anderson, P. L. Schwartzberg, and F. Candotti The expression of Wiskott-Aldrich syndrome protein (WASP) is dependent on WASP-interacting protein (WIP) Int. Immunol., February 1, 2007; 19(2): 185 - 192. [Abstract] [Full Text] [PDF] S. Trifari, G. Sitia, A. Aiuti, S. Scaramuzza, F. Marangoni, L. G. Guidotti, S. Martino, P. Saracco, L. D. Notarangelo, M.-G. Roncarolo, et al. Defective Th1 Cytokine Gene Transcription in CD4+ and CD8+ T Cells from Wiskott-Aldrich Syndrome Patients J. Immunol., November 15, 2006; 177(10): 7451 - 7461. [Abstract] [Full Text] [PDF] T. Neff, B. C. Beard, and H.-P. Kiem Survival of the fittest: in vivo selection and stem cell gene therapy Blood, March 1, 2006; 107(5): 1751 - 1760. [Abstract] [Full Text] [PDF] S. Burns, G. O. Cory, W. Vainchenker, and A. J. Thrasher Mechanisms of WASp-mediated hematologic and immunologic disease Blood, December 1, 2004; 104(12): 3454 - 3462. [Abstract] [Full Text] [PDF] M. V. Evans-Galea, M. M. Wielgosz, T. S. Strom, H. Hanawa, J. M. Cunningham, and A. W. Nienhuis Developing Lentiviral Vectors for Gene Therapy of Wiskott-Aldrich Syndrome. Blood (ASH Annual Meeting Abstracts), November 16, 2004; 104(11): 3170 - 3170. [Abstract] H. Hanawa, P. Hematti, K. Keyvanfar, M. E. Metzger, A. Krouse, R. E. Donahue, S. Kepes, J. Gray, C. E. Dunbar, D. A. Persons, et al. Efficient gene transfer into rhesus repopulating hematopoietic stem cells using a simian immunodeficiency virus-based lentiviral vector system Blood, June 1, 2004; 103(11): 4062 - 4069. [Abstract] [Full Text] [PDF]

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