In utero gene transfer of human factor IX to fetal mice can induce postnatal tolerance of the exogenous clotting factor
Waddington SN, Buckley SM, Nivsarkar M, Jezzard S, Schneider H, Dahse T, Kemball-Cook G, Miah M, Tucker N, Dallman MJ, Themis M, Coutelle C (2003)
Publication Type: Journal article, Original article
Publication year: 2003
Journal
Book Volume: 101
Pages Range: 1359-1366
Journal Issue: 4
DOI: 10.1182/blood-2002-03-0779
Abstract
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.
Authors with CRIS profile
Holm Schneider
Lehrstuhl für Experimentelle Medizin mit dem Schwerpunkt Molekulare Pathogeneseforschung
Involved external institutions
United Kingdom (GB)How to cite
APA:
Waddington, S.N., Buckley, S.M., Nivsarkar, M., Jezzard, S., Schneider, H., Dahse, T.,... Coutelle, C. (2003). In utero gene transfer of human factor IX to fetal mice can induce postnatal tolerance of the exogenous clotting factor. Blood, 101(4), 1359-1366. https://doi.org/10.1182/blood-2002-03-0779
MLA:
Waddington, Simon N., et al. "In utero gene transfer of human factor IX to fetal mice can induce postnatal tolerance of the exogenous clotting factor." Blood 101.4 (2003): 1359-1366.
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