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Selective uptake of naked vaccine RNA by dendritic cells is driven by macropinocytosis and abrogated upon DC maturation

Gene Therapy volume 18, pages 702–708 (2011)Cite this article

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Abstract

Even though it is known for more than one decade that antigen-encoding RNA can deliver antigenic information to induce antigen-specific immunity against cancer, the nature and mechanism of RNA uptake have remained enigmatic. In this study, we investigated the pharmacokinetics of naked RNA administered into the lymph node. We observed that RNA is rapidly and selectively uptaken by lymph node dendritic cells (DCs). Furthermore, in vitro and in vivo studies revealed that the efficient internalization of RNA by human and murine DCs is primarily driven by macropinocytosis. Selective inhibition of macropinocytosis by compounds or as a consequence of DC maturation abrogated RNA internalization and delivery of encoded antigens. Our findings imply that bioavailability of recombinant RNA vaccines in vivo highly depends on the density and the maturation stage of DCs at the administration site and are of importance for the design of RNA-based clinical immunotherapy protocols.

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Acknowledgements

We thank Marc Holzmann for excellent assistance. This work was supported by the Combined Project Grant SFB 432 and by the GO-Bio funding of the Federal Ministry of Education and Research (BMBF).

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Author notes

  1. M Diken, S Kreiter and A Selmi: These authors contributed equally to this work and shared the first authorship.

  2. Ö Türeci and U Sahin: These authors contributed equally to this work and shared the last authorship.

Authors and Affiliations

  1. Institute for Translational Oncology and Immunology (TRON), Mainz, Germany

    M Diken, S Kreiter, A Selmi & U Sahin

  2. Division of Translational and Experimental Oncology, Department of Internal Medicine III, Johannes Gutenberg University, Mainz, Germany

    C M Britten & U Sahin

  3. Ribological, BioNTech AG, Mainz, Germany

    C M Britten, C Huber & U Sahin

  4. Ganymed Pharmaceuticals AG, Mainz, Germany

    Ö Türeci

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  1. M Diken
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  2. S Kreiter
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Correspondence to U Sahin.

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Competing interests

U Sahin (co-founder, chief executive officer), C Huber (co-founder) and CM Britten (employee) are associated with Ribological, BioNTech AG (Mainz, Germany), a company, which develops RNA-based cancer vaccines. U Sahin, S Kreiter, Ö Tureci and A Selmi are inventors on a patent application, in which parts of this paper are covered.

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Diken, M., Kreiter, S., Selmi, A. et al. Selective uptake of naked vaccine RNA by dendritic cells is driven by macropinocytosis and abrogated upon DC maturation. Gene Ther 18, 702–708 (2011). https://doi.org/10.1038/gt.2011.17

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  • DOI: https://doi.org/10.1038/gt.2011.17

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