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Prepublished online as a Blood First Edition Paper on September 5, 2002; DOI 10.1182/blood-2002-07-2131. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-07-2131v1 101/2/485    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 Gough, P. J. Articles by Raines, E. W. Search for Related Content PubMed PubMed Citation Articles by Gough, P. J. Articles by Raines, E. W. Related Collections Phagocytes Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 January 2003, Vol. 101, No. 2, pp. 485-491 GENE THERAPY Gene therapy of apolipoprotein E-deficient mice using a novel macrophage-specific retroviral vector Peter J. Gough and Elaine W. Raines From the Department of Pathology, University of Washington, Seattle. The use of retroviral gene transfer into hematopoietic stem cells for human gene therapy has been hampered by the absence of retroviral vectors that can generate long-lasting, lineage-specific gene expression. We developed self-inactivating retroviral vectors that incorporate gene-regulatory elements from the macrophage-restricted human CD68 gene. Through the transplantation of transduced murine hematopoietic stem cells (HSCs), we show that a vector incorporating a 342-base pair (bp) fragment of 5' flanking sequence from the CD68 gene, in addition to the CD68 first intron, was able to direct macrophage-specific expression of an enhanced green fluorescent protein (EGFP) reporter gene in inflammatory cell exudates and lymphoid organs in vivo. Levels of EGFP expression generated by this vector were greater than those generated by a standard Moloney murine leukemia retroviral vector, and they were stable for at least a year after transplantation of transduced HSCs. To evaluate the ability of this vector to generate therapeutically useful levels of gene expression, we transplanted apolipoprotein E (ApoE)-deficient HSCs transduced with a virus encoding ApoE into ApoE-deficient mice. Macrophages from these mice expressed levels of ApoE that were comparable to those from wild-type mice, and vector-driven expression of ApoE in macrophages was sufficient to reverse both hypercholesterolemia and atherosclerotic lesion development. The future application of this retroviral vector should provide a powerful tool to further elucidate macrophage function and for human gene therapy. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. R. Su, J. L. Blakemore, Y. Zhang, M. F. Linton, and S. Fazio Lentiviral Transduction of ApoAI Into Hematopoietic Progenitor Cells and Macrophages: Applications to Cell Therapy of Atherosclerosis Arterioscler. Thromb. Vasc. Biol., August 1, 2008; 28(8): 1439 - 1446. [Abstract] [Full Text] [PDF] B. E. Wisse, K. Ogimoto, J. Tang, M. K. Harris Jr., E. W. Raines, and M. W. 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Bostrom, B. B. Boyanovsky, C. T. Jordan, M. P. Wadsworth, D. J. Taatjes, F. C. de Beer, and N. R. Webb Group V Secretory Phospholipase A2 Promotes Atherosclerosis: Evidence From Genetically Altered Mice Arterioscler. Thromb. Vasc. Biol., March 1, 2007; 27(3): 600 - 606. [Abstract] [Full Text] [PDF] K. S. Meir and E. Leitersdorf Atherosclerosis in the Apolipoprotein E-Deficient Mouse: A Decade of Progress Arterioscler. Thromb. Vasc. Biol., June 1, 2004; 24(6): 1006 - 1014. [Abstract] [Full Text] [PDF] P. J. Gough, K. J. Garton, P. T. Wille, M. Rychlewski, P. J. Dempsey, and E. W. Raines A Disintegrin and Metalloproteinase 10-Mediated Cleavage and Shedding Regulates the Cell Surface Expression of CXC Chemokine Ligand 16 J. Immunol., March 15, 2004; 172(6): 3678 - 3685. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020