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Minicircle: Next Generation DNA Vectors for Vaccination

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Gene Therapy of Solid Cancers

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1317))

Abstract

The use of DNA vaccines requires pharmaceutical grade DNA that causes the immunization on the basis of a nucleic acid sequence that encodes the protein to be vaccinated against. This nucleic acid sequence can be a circular or linear plasmid, preferably a double stranded one and should not contain any other and especially not any “toxic” sequences. Sequences that are not desirable to be part of the DNA drug can be those deriving from the (typically) bacterial amplification system to produce the DNA vaccine. These could be those portions of a plasmid that are only used for controlling the bacterial replication of the plasmid or those used to select for the plasmid during cloning or even worse during production. After initial approaches to avoid the presence of these sequences in DNA vaccine plasmids with “mini-plasmids,” a significant improvement in product safety was obtained by use of minicircles—circular and ccc-supercoiled expression cassettes of the DNA vaccine. Initial results proofed their extremely high expression level and recent comparison of DNA vaccines based on either plasmid or minicircle DNA show successful vaccination against HBV in mice, as shown in this overview chapter.

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Acknowledgement

We thank the research team of PlasmidFactory, Bielefeld, Germany for critical discussion and contributing work and Janine Conde-Lopez for support with figures; the German Federal Ministry of Education and Research (BMBF) for grants BioChancePLUS (0313749) and Nano-4-Life (13N9063). Part of this work has also been supported by the CliniGene Network of Excellence funded by the European Commission FP6 Research Programme under contract LSHB-CT-2006-018933.

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Authors and Affiliations

  1. PlasmidFactory GmbH & Co. KG, Meisenstr. 96, 33607, Bielefeld, Germany

    Martin Schleef & Marco Schmeer

  2. Department of Internal Medicine I, University Hospital Ulm, Albert Einstein Allee 23, 89081, Ulm, Germany

    R. Schirmbeck & Michael Reiser

  3. Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, Charlestown, MA, 02129, USA

    Michael Reiser

  4. Department of Virology, Institut Pasteur, 28, rue du Docteur Roux, 75724, Paris Cedex 15, France

    Marie-Louise Michel

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  1. Martin Schleef
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  2. R. Schirmbeck
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  3. Michael Reiser
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  4. Marie-Louise Michel
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  5. Marco Schmeer
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Corresponding author

Correspondence to Martin Schleef .

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Editors and Affiliations

  1. Translational Oncology of Solid Tumors, Experimental and Clinical Research Center, Charité University Medicine Berlin and Max-Delbrück-Center for Molecular Medicine, Berlin, Germany

    Wolfgang Walther

  2. Translational Oncology of Solid Tumors, Experimental and Clinical Research Center, Charité University Medicine Berlin and Max-Delbrück-Center for Molecular Medicine, Berlin, Berlin, Germany

    Ulrike Stein

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Schleef, M., Schirmbeck, R., Reiser, M., Michel, ML., Schmeer, M. (2015). Minicircle: Next Generation DNA Vectors for Vaccination. In: Walther, W., Stein, U. (eds) Gene Therapy of Solid Cancers. Methods in Molecular Biology, vol 1317. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2727-2_18

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  • DOI: https://doi.org/10.1007/978-1-4939-2727-2_18

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2726-5

  • Online ISBN: 978-1-4939-2727-2

  • eBook Packages: Springer Protocols

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