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Foamy virus–adenovirus hybrid vectors

Gene Therapy volume 11, pages 722–728 (2004)Cite this article

Abstract

To confer adenovirus vectors (AdV), the feature of integration into the host cell genome hybrid vectors were characterized in vitro, which express vectors derived from the prototypic foamy virus (FV) in the backbone of a high-capacity AdV. FVs constitute a subfamily of retroviruses with a distinct replication pathway and no known pathogenicity. In the absence of envelope glycoprotein, the prototypic FV behaves like a retrotransposon, while it behaves like an exogenous retrovirus in its presence. Two principle types of vectors, which either allows the intracellular (HC-FAD-7) or, in addition, the extracellular (HC-FAD-2) pathway were constructed. In both chimeras the expression of the FV vector was controlled by the tetracycline-regulatable system. Hybrids were produced close to 1010 infectious units/ml. By Southern blotting, the functionality of the hybrid vectors to generate host cell genomic integrants was shown. However, the efficiency of HC-FAD-7 to establish stable transgene expression was rather low, while around 70% of cells were stably transduced in secondary round following primary transduction with HC-FAD-2 at an MOI of 100. Given the benign characteristics of high-capacity adenovirus and FV vectors, hybrids based on HC-FAD-2 are probably suited for an in vivo application.

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Acknowledgements

This work was supported by grants from the BMBF (BEO 0312191), Sächsisches Staatsministerium für Umwelt und Landwirtschaft (66-8802.5327/62 and 13-8811.61/142), DFG (Re 627/6-3 and Europäisches Graduiertenkolleg ‘Gene regulation in and by microbial pathogens’) Bayerische Forschungsstiftung (Forgen), and EU (BMH4-CT97-2010). FK was supported by the Boehringer Ingelheim Foundation. We thank Frank Graham for providing the helper virus AdLC8cluc.

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Authors and Affiliations

  1. Institut für Virologie und Immunbiologie, Universität, Würzburg, Germany

    M Picard-Maureau, A Rethwilm & M Heinkelein

  2. Germany and Division of Gene Therapy, Zentrum für Molekulare Medizin, Universität Köln, Universität Ulm, Germany

    F Kreppel & S Kochanek

  3. Institut für Virologie, Medizinische Fakultät ‘Carl Gustav Carus’, Technische Universität, Dresden, Germany

    D Lindemann, T Juretzek, O Herchenröder & A Rethwilm

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  1. M Picard-Maureau
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  2. F Kreppel
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Picard-Maureau, M., Kreppel, F., Lindemann, D. et al. Foamy virus–adenovirus hybrid vectors. Gene Ther 11, 722–728 (2004). https://doi.org/10.1038/sj.gt.3302216

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