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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 Chao, H. Articles by Walsh, C. E. Search for Related Content PubMed PubMed Citation Articles by Chao, H. Articles by Walsh, C. E. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 May 2001, Vol. 97, No. 10, pp. 3311-3312 BRIEF REPORT Induction of tolerance to human factor VIII in mice Hengjun Chao and Christopher E. Walsh From the University of North Carolina Gene Therapy Center and the Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC. This paper reports loss of human factor VIII (hFVIII) inhibitory antibody in immunocompetent C57BL/6 mice. High-titer anti-hFVIII antibody developed in the mice within 7 to 14 days of intraportal administration of adeno-associated virus (AAV) carrying FVIII that coincided with a reduction in plasma hFVIII antigen. Bethesda titers (> 100 units) persisted relatively unchanged for 9 to 10 months. Unexpectedly, at 10 months after injection of the virus, hFVIII protein (up to 59 ng/mL) was detected in 3 mice at the same time as disappearance of hFVIII inhibitor. The level of hFVIII was similar to that found in immunodeficient mice receiving the same dose of recombinant AAV carrying hFVIII without hFVIII inhibitor. These results suggest that tolerance to hFVIII can be induced by sustained expression of hFVIII in a mouse model. Further elucidation of this observation may affect use of FVIII gene transfer in the treatment of inhibitor-positive patients with hemophilia A. © 2001 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: H. Jiang, D. Lillicrap, S. Patarroyo-White, T. Liu, X. Qian, C. D. Scallan, S. Powell, T. Keller, M. McMurray, A. Labelle, et al. Multiyear therapeutic benefit of AAV serotypes 2, 6, and 8 delivering factor VIII to hemophilia A mice and dogs Blood, July 1, 2006; 108(1): 107 - 115. [Abstract] [Full Text] [PDF] E. Dobrzynski and R. W. Herzog Tolerance Induction by Viral In Vivo Gene Transfer Clin. Med. Res., November 1, 2005; 3(4): 234 - 240. [Abstract] [Full Text] [PDF] R. Sarkar, R. Tetreault, G. Gao, L. Wang, P. Bell, R. Chandler, J. M. Wilson, and H. H. Kazazian Jr Total correction of hemophilia A mice with canine FVIII using an AAV 8 serotype Blood, February 15, 2004; 103(4): 1253 - 1260. [Abstract] [Full Text] [PDF] G. A. Palmer, J. L. Brogdon, S. L. Constant, and P. Tattersall A Nonproliferating Parvovirus Vaccine Vector Elicits Sustained, Protective Humoral Immunity following a Single Intravenous or Intranasal Inoculation J. Virol., February 1, 2004; 78(3): 1101 - 1108. [Abstract] [Full Text] [PDF] T. VandenDriessche Challenges and progress in gene therapy for hemophilia A Blood, September 15, 2003; 102(6): 1938 - 1939. [Full Text] [PDF] C. D. Scallan, D. Lillicrap, H. Jiang, X. Qian, S. L. Patarroyo-White, A. E. Parker, T. Liu, J. Vargas, D. Nagy, S. K. Powell, et al. Sustained phenotypic correction of canine hemophilia A using an adeno-associated viral vector Blood, September 15, 2003; 102(6): 2031 - 2037. [Abstract] [Full Text] [PDF] B. D. Brown and D. Lillicrap Dangerous liaisons: the role of "danger" signals in the immune response to gene therapy Blood, July 30, 2002; 100(4): 1133 - 1140. [Abstract] [Full Text] [PDF]

	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020