SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on July 17, 2003; DOI 10.1182/blood-2003-03-0962. This Article 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 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. Social Bookmarking                   What's this? Submitted March 28, 2003 Accepted June 4, 2003 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* Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA; Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA Division of Research Immunology/BMT, Children's Hospital Los Angeles, Los Angeles, CA, USA University of Southern Califnornia School of Medicine, Los Angeles, CA, USA * Corresponding author; email: hkiem{at}fhcrc.org. 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 three animals with GFP selected cells, half of which had been transduced with either SAR, or non SAR-containing retrovirus vectors. All animals showed delayed engraftment compared to 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 2-9-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 which may obviate the need for multi-copy 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]

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