SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on October 3, 2002; DOI 10.1182/blood-2002-03-0779. This Article Full Text Full Text (PDF) Erratum (v107,p1750) All Versions of this Article: 2002-03-0779v1 101/4/1359    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 Waddington, S. N. Articles by Coutelle, C. Search for Related Content PubMed PubMed Citation Articles by Waddington, S. N. Articles by Coutelle, C. Related Collections Hemostasis, Thrombosis, and Vascular Biology Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 February 2003, Vol. 101, No. 4, pp. 1359-1366 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY In utero gene transfer of human factor IX to fetal mice can induce postnatal tolerance of the exogenous clotting factor Simon N. Waddington, Suzanne M. K. Buckley, Megha Nivsarkar, Sarah Jezzard, Holm Schneider, Thomas Dahse, Geoff Kemball-Cook, Maznu Miah, Nick Tucker, Margaret J. Dallman, Mike Themis, and Charles Coutelle From the Gene Therapy, Section of Cell and Molecular Biology, and Department of Biological Sciences, Imperial College School of Science, Technology and Medicine, London, United Kingdom; Childrens Hospital, University of Erlangen-Nuernberg, Erlangen, Germany; and MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, London, United Kingdom. The fundamental hypotheses behind fetal gene therapy are that it may be possible (1) to achieve immune tolerance of transgene product and, perhaps, vector; (2) to target cells and tissues that are inaccessible in adult life; (3) to transduce a high percentage of rapidly proliferating cells, and in particular stem cells, with relatively low absolute virus doses leading to clonal transgene amplification by integrating vectors; and (4) to prevent early disease manifestation of genetic diseases. This study provides evidence vindicating the first hypothesis; namely, that intravascular prenatal administration of an adenoviral vector carrying the human factor IX (hFIX) transgene can induce immune tolerance of the transgenic protein. Following repeated hFIX protein injection into adult mice, after prenatal vector injection, we found persistence of blood hFIX and absence of hFIX antibodies in 5 of 9 mice. Furthermore, there was substantial hFIX expression after each of 2 reinjections of vector without detection of hFIX antibodies. In contrast, all adult mice that had not been treated prenatally showed a rapid loss of the injected hFIX and the development of high hFIX antibody levels, both clear manifestations of a strong immune reaction. © 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: N. Mackman Tissue-Specific Hemostasis in Mice Arterioscler Thromb Vasc Biol, November 1, 2005; 25(11): 2273 - 2281. [Abstract] [Full Text] [PDF] S. N. Waddington, M. S. Nivsarkar, A. R. Mistry, S. M. K. Buckley, G. Kemball-Cook, K. L. Mosley, K. Mitrophanous, P. Radcliffe, M. V. Holder, M. Brittan, et al. Permanent phenotypic correction of hemophilia B in immunocompetent mice by prenatal gene therapy Blood, November 1, 2004; 104(9): 2714 - 2721. [Abstract] [Full Text] [PDF] E. Dobrzynski, F. Mingozzi, Y.-L. Liu, E. Bendo, O. Cao, L. Wang, and R. W. Herzog Induction of antigen-specific CD4+ T-cell anergy and deletion by in vivo viral gene transfer Blood, August 15, 2004; 104(4): 969 - 977. [Abstract] [Full Text] [PDF]

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