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Click-Shielded and Targeted Lipopolyplexes

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Oligonucleotide-Based Therapies

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2036))

Abstract

Lipopolyplexes present well-established nucleic acid carriers assembled from sequence-defined cationic lipo-oligomers and DNA or RNA. They can be equipped with additional surface functionality, like shielding and targeting, in a stepwise assembly method using click chemistry. Here, we describe the synthesis of the required compounds, an azide-bearing lipo-oligomer structure and dibenzocyclooctyne (DBCO) click agents as well as the assembly of the compounds with siRNA into a surface-functionalized formulation. Both the lipo-oligomer and the DBCO-equipped shielding and targeting agents are produced by solid-phase synthesis (SPS). This enables for precise variation of all functional units, like variation in the amount of DBCO attachment sites or polyethylene glycol (PEG) length. Special cleavage conditions with only 5% trifluoroacetic acid (TFA) must be applied for the synthesis of the shielding and targeting agents due to acid lability of the DBCO unit. The two-step lipopolyplex assembly technique allows for separate optimization of the core and the shell of the formulation.

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Acknowledgments

This work was supported by DFG SFB1032 B4 (P.K. and E.W.), SFB1066 B5 (P.K. and E.W.), and DFG Excellence Cluster Nanosystems Initiative Munich (E.W.).

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Authors and Affiliations

  1. Pharmaceutical Biotechnology, Center for System-based Drug Research, Ludwig-Maximilians-Universität München, Munich, Germany

    Philipp Michael Klein & Ernst Wagner

  2. Nanosystems Initiative Munich, Munich, Germany

    Ernst Wagner

Authors
  1. Philipp Michael Klein
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  2. Ernst Wagner
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Editor information

Editors and Affiliations

  1. Center for Advanced Therapies, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden

    Olof Gissberg

  2. Center for Advanced Therapies, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden

    Rula Zain

  3. Center for Advanced Therapies, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden

    Karin E. Lundin

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Klein, P.M., Wagner, E. (2019). Click-Shielded and Targeted Lipopolyplexes. In: Gissberg, O., Zain, R., Lundin, K. (eds) Oligonucleotide-Based Therapies. Methods in Molecular Biology, vol 2036. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9670-4_8

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  • DOI: https://doi.org/10.1007/978-1-4939-9670-4_8

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9669-8

  • Online ISBN: 978-1-4939-9670-4

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