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Delivery of functional DNA and messenger RNA to mammalian phagocytic cells by recombinant yeast

Gene Therapy volume 19, pages 237–245 (2012)Cite this article

Abstract

Among the different vaccination approaches, DNA/RNA vaccination represents a promising means in particular for the induction of effective cellular immune responses conferred by CD8-positive T lymphocytes. To achieve such immune responses, there is a need for novel delivery systems that allow the introduction of nucleic acids to the cytosol of immune cells. We show, for the first time, the delivery of functional DNA and messenger RNA (mRNA) to mammalian antigen-presenting cells, including murine macrophages and human dendritic cells, using the yeast Saccharomyces cerevisiae as the delivery vehicle. After transfer of the particular nucleic acid, subsequent antigen processing and presentation were demonstrated in a human system. Remarkably, release of DNA/mRNA does not require additional ‘helper’ proteins such as listeriolysin. In conclusion, the yeast-based system described here is superior to many bacterial and viral systems in terms of efficacy, safety and targeting suggesting ‘mycofection’ as a promising approach for the development of a novel type of live vaccines.

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Acknowledgements

We thank Birgit Glombitza and Roswitha Schepp for excellent technical assistance. We are grateful to the Winterbergkliniken Saarbrücken for providing blood cell concentrates, Andreas Meyerhans for a pp65-containing plasmid, and Gernot Geginat for the IC21 cell line and helpful discussions. This work was supported by a start-up grant from Saarland University and a grant from the ARGUS Foundation, Berlin, Germany, to FB.

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  1. T Breinig

    Present address: Present address: Department of Computer Science, Saarland University, Building E1.3, 66123 Saarbrücken, Germany.,

Authors and Affiliations

  1. Molecular and Cell Biology, Saarland University, Saarbrücken, Germany

    B Walch, M J Schmitt & F Breinig

  2. Department of Virology, Junior research group for Virology/Immunology, Saarland University Hospital, Homburg, Germany

    T Breinig

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Correspondence to F Breinig.

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Walch, B., Breinig, T., Schmitt, M. et al. Delivery of functional DNA and messenger RNA to mammalian phagocytic cells by recombinant yeast. Gene Ther 19, 237–245 (2012). https://doi.org/10.1038/gt.2011.121

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