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This Article Full Text Full Text (PDF) 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 Wang, J.-M. Articles by Kurachi, K. Search for Related Content PubMed PubMed Citation Articles by Wang, J.-M. Articles by Kurachi, K. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Persistent Systemic Production of Human Factor IX in Mice by Skeletal Myoblast-Mediated Gene Transfer: Feasibility of Repeat Application to Obtain Therapeutic Levels Jian-Min Wang, Hong Zheng, Mila Blaivas, and Kotoku Kurachi From the Department of Human Genetics, and the Department of Pathology, University of Michigan Medical School, Ann Arbor, MI. Myoblast-mediated gene transfer and its repeated applications were tested for achieving a long-term stable systemic production of human factor IX (hFIX) at a therapeutic level in SCID mice. Primary skeletal myoblasts were stably transfected with a hFIX expression plasmid vector, pdLMe4AhIXm1, which contains a hFIX minigene under the control of a -actin promoter with muscle creatine kinase enhancers. Myotubes derived from the myoblasts produced 1,750 ng hFIX/106 cells/24 hours in culture. hFIX secretion by the myoblasts and thereof derived myotubes were equally efficient, and myotubes were shown to have a sufficient secretory capacity to handle a substantially elevated production of hFIX. After intramuscular injection of 5, 10, and 20 × 106 myoblasts, SCID mice stably produced hFIX into the systemic circulation proportional to the number of implanted cells, and the expression levels were maintained for at least up to 10 months (end of the experiment). Additional cell injections administered to animals that originally received 10 × 106 cells approximately 2 months later elevated the systemic hFIX levels to an average of 182 ± 21 ng/mL, a therapeutic level, which persisted for at least 8 months (end of the experiment). These results indicate that long-term, stable systemic production of hFIX at therapeutic levels can be achieved by repeated application of myoblast-mediated gene transfer. Blood, Vol. 90 No. 3 (August 1), 1997: pp. 1075-1082 © 1997 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: A. K. Malik, P. E. Monahan, D. L. Allen, B.-G. Chen, R. J. Samulski, and K. Kurachi Kinetics of Recombinant Adeno-Associated Virus-Mediated Gene Transfer J. Virol., April 15, 2000; 74(8): 3555 - 3565. [Abstract] [Full Text] J. N. Lozier, M. E. Metzger, R. E. Donahue, and R. A. Morgan The Rhesus Macaque as an Animal Model for Hemophilia B Gene Therapy Blood, March 15, 1999; 93(6): 1875 - 1881. [Abstract] [Full Text] [PDF] H. Nakai, R. W. Herzog, J. N. Hagstrom, J. Walter, S.-H. Kung, E. Y. Yang, S. J. Tai, Y. Iwaki, G. J. Kurtzman, K. J. Fisher, et al. Adeno-Associated Viral Vector-Mediated Gene Transfer of Human Blood Coagulation Factor IX Into Mouse Liver Blood, June 15, 1998; 91(12): 4600 - 4607. [Abstract] [Full Text] [PDF]

	Copyright © 1997 by American Society of Hematology         Online ISSN: 1528-0020