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Incorporation of decay-accelerating factor into the baculovirus envelope generates complement-resistant gene transfer vectors

Nature Biotechnology volume 19, pages 451–455 (2001)Cite this article

Abstract

Baculovirus vectors are an efficient means to deliver genes into hepatocytes in vitro. In experiments that exclude components of the complement system, gene transfer is facilitated. Therefore, the complement system has been defined to represent a potent primary barrier to direct application of baculoviruses in vivo. Here we have genetically manipulated baculoviruses so that the complement-regulatory protein human decay- accelerating factor (DAF) is incorporated into the viral envelope. We found that this modification protected baculovirus vectors against complement-mediated inactivation. Complement-resistant baculovirus vectors were additionally analyzed by immunoblotting and electron microscopy, showing the extent of envelope-incorporated DAF and shape of complement-resistant baculoviruses after exposure to complement. This modified baculovirus vector allowed for an enhanced gene transfer into complement-sufficient neonatal rats in vivo, and thus represents a step in the development of improved alternative viral vectors for gene therapy.

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Figure 1: Complement-assay using Sf9 insect cells.
Figure 2: DAF-modified baculoviruses transfer genes into Huh7 cells in the presence of complement.
Figure 3: Immunoblot of purified recombinant baculoviruses.
Figure 4: Electron-microscopic analysis of recombinant baculoviruses.
Figure 5: Baculovirus-mediated gene transfer of the hFIX gene in vivo.

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Acknowledgements

We dedicate this work to the memory of Michael Strauss. The authors thank John Atkinson and Kathy Liszewski for the DAF cDNA, Mark Kay for the hFIX cDNA, and Peter Faulkner for AcV5 antibodies. We also wish to acknowledge Verena Sladek, Uta Fischer, Dagmar Viertel, and Gabi N′diaye for excellent technical assistance. This work was supported by the Bundesministerium für Bildung und Forschung (BMBF Gesundheitsforschung 2000, no. 01GE9628).

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Authors and Affiliations

  1. DeveloGen AG Berlin, Robert-Rössle-Str. 10, Berlin, D-13125, Germany

    Andreas Hüser & Christian Hofmann

  2. Institut für Zoo- und Wildtierforschung, Alfred-Kowalke-Str. 17, Berlin, D-10315, Germany

    Michael Rudolph

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  1. Andreas Hüser
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Correspondence to Christian Hofmann.

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Hüser, A., Rudolph, M. & Hofmann, C. Incorporation of decay-accelerating factor into the baculovirus envelope generates complement-resistant gene transfer vectors. Nat Biotechnol 19, 451–455 (2001). https://doi.org/10.1038/88122

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