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32nd Hemophilia Symposium pp 72–80Cite as

Adenovirus-mediated regulatable Expression of human Factor IX in vitro and in vivo

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Abstract

The ability to modulate transgene expression in vivo not only will mimic the expression of endogenous genes but is also important for therapeutic and safety reasons in gene therapy protocols. Regulated gene expression systems should be able to induce long-term expression and allow for exogenous control of expression. For this aim, the high gene transfer capacity of adenoviral vectors (Ad) and the high inducibility of the tetracycline-regulatable systems were combined in this study to develop a tetracycline-regulatable Ad vector for expression of human factor IX (hFIX). In vitro studies showed a dose dependent and high induction potential of the hFIX expression system resulting in 65-fold increase in hFIX expression after induction with doxycycline. The use of a liver-specific promoter has been shown to induce a relatively high expression of hFIX compared to CMV promoter in HepG2. In contrast to this, the liver specific promoter showed no hFIX expression when tested in three other non-hepatic human cell lines. The expression of hFIX can either be maintained by continuous induction of doxycycline or up- and down-regulated by mutual presence and absence of doxycycline. When mice were injected with Ad vector for hFIX and induced by doxycycline they showed a therapeutic level of circulating hFIX for one week. These results report on the development of a regulated Ad vectors for the expression of hFIX and demonstrate that FIX gene expression is regulatable in vitro and in vivo. These vectors should be useful not only for gene therapy protocols in haemophilia B but also for diverse applications in gene therapy studies.

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Authors
  1. M. A. Srour
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  2. H. Fechner
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  3. X. Wang
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  4. U. Siemetzki
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  5. T. Albert
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  6. J. Oldenburg
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  7. P. Hanfland
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  8. W. Poller
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  9. H.-H. Brackmann
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  10. R. Schwaab
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Editor information

Editors and Affiliations

  1. Hemophilia Center, Dept. of Internal Medicine, University Hospital, Theodor-Stern-Kai 7, D-60590, Frankfurt am Main, Germany

    Inge Scharrer

  2. Dept. of Hemostasiology, University Hospital, Ziemssenstr. 1a, D-80336, München, Germany

    Wolfgang Schramm

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© 2003 Springer-Verlag Berlin Heidelberg

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Srour, M.A. et al. (2003). Adenovirus-mediated regulatable Expression of human Factor IX in vitro and in vivo . In: Scharrer, I., Schramm, W. (eds) 32nd Hemophilia Symposium. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-18150-4_9

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  • DOI: https://doi.org/10.1007/978-3-642-18150-4_9

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-43884-7

  • Online ISBN: 978-3-642-18150-4

  • eBook Packages: Springer Book Archive

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