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Blood, 1 November 2003, Vol. 102, No. 9, pp. 3117-3119. Prepublished online as a Blood First Edition Paper on July 17, 2003; DOI 10.1182/blood-2003-03-0962. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-03-0962v1 102/9/3117    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 Kurre, P. Articles by Kiem, H.-P. Search for Related Content PubMed PubMed Citation Articles by Kurre, P. Articles by Kiem, H.-P. Related Collections Hematopoiesis and Stem Cells Brief Reports Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Brief report Scaffold attachment region–containing retrovirus vectors improve long-term proviral expression after transplantation of GFP-modified CD34+ baboon repopulating cells Peter Kurre, Julia Morris, Bobbie Thomasson, Donald B. Kohn, and Hans-Peter Kiem From the Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; the Departments of Pediatrics and Medicine, University of Washington School of Medicine, Seattle, WA; the Division of Research Immunology/Bone Marrow Transplantation, Children's Hospital Los Angeles, Los Angeles, CA; and the University of Southern California Keck School of Medicine, Los Angeles, CA. Sustained high-level proviral expression is important for clinical applications of gene therapy. Genetic elements including the -interferon scaffold attachment region (SAR) have been shown to improve transgene expression in hematopoietic cells. We hypothesized that SAR elements might improve expression and allow the preselection of successfully transduced cells. Thus, we transplanted green fluorescent protein (GFP)–selected cells, half of which had been transduced with either SAR or non–SAR-containing retrovirus vectors, into 3 animals. All animals showed delayed engraftment compared with historic controls (28 vs 15.5 days). GFP marking was seen at levels up to 8% but declined over the first 6 weeks. Importantly, fluorescence intensity was 2- to 9-fold increased in progeny of SAR versus non–SAR vector–modified cells in all hematopoietic lineages for the duration of follow-up (6-12 months). In conclusion, the use of SAR-containing vectors improved transgene expression in hematopoietic repopulating cells, which may obviate the need for multicopy integration to achieve high-level expression and reduce the risk for insertional mutagenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. E. Shepherd, H.-P. Kiem, P. M. Lansdorp, C. E. Dunbar, G. Aubert, A. LaRochelle, R. Seggewiss, P. Guttorp, and J. L. Abkowitz Hematopoietic stem-cell behavior in nonhuman primates Blood, September 15, 2007; 110(6): 1806 - 1813. [Abstract] [Full Text] [PDF] R. E. Donahue, I. S. Y. Chen, J. C. Morris, and H.-P. Kiem Transgene-specific tolerance versus immune response Blood, September 1, 2004; 104(5): 1578 - 1579. [Full Text] [PDF] 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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