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Cell-Penetrating Peptides Delivering siRNAs: An Overview

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Design and Delivery of SiRNA Therapeutics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2282))

Abstract

Cell-Penetrating Peptides (CPP) are valuable tools capable of crossing the plasma membrane to deliver therapeutic cargo inside cells. Small interfering RNAs (siRNA) are double-stranded RNA molecules capable of silencing the expression of a specific protein triggering the RNA interference (RNAi) pathway, but they are unable to cross the plasma membrane and have a short half-life in the bloodstream. In this overview, we assessed the many different approaches used and developed in the last two decades to deliver siRNA through the plasma membrane through different CPPs sorted according to three different loading strategies: covalent conjugation, complex formation, and CPP-decorated (functionalized) nanocomplexes. Each of these strategies has pros and cons, but it appears the latter two are the most commonly reported and emerging as the most promising strategies due to their simplicity of synthesis, use, and versatility. Recent progress with siRNA delivered by CPPs seems to focus on targeted delivery to reduce side effects and amount of drugs used, and it appears to be among the most promising use for CPPs in future clinical applications.

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Acknowledgements

This work was supported by Swedish Research Council.

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Authors and Affiliations

  1. Department of Biochemistry and Biophysics, Arrhenius Laboratories for Natural Sciences, Stockholm University, Stockholm, Sweden

    Luca Falato, Maxime Gestin & Ülo Langel

  2. Laboratory of Molecular Biotechnology, Institute of Technology, University of Tartu, Tartu, Estonia

    Ülo Langel

Authors
  1. Luca Falato
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  2. Maxime Gestin
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  3. Ülo Langel
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Corresponding author

Correspondence to Luca Falato .

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Editors and Affiliations

  1. Department of Oncology, Odense University Hospital Odense, Denmark, Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark

    Henrik J. Ditzel

  2. Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark

    Martina Tuttolomondo

  3. Center for RNA Medicine, Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark

    Sakari Kauppinen

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Falato, L., Gestin, M., Langel, Ü. (2021). Cell-Penetrating Peptides Delivering siRNAs: An Overview. In: Ditzel, H.J., Tuttolomondo, M., Kauppinen, S. (eds) Design and Delivery of SiRNA Therapeutics. Methods in Molecular Biology, vol 2282. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1298-9_18

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  • DOI: https://doi.org/10.1007/978-1-0716-1298-9_18

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  • Publisher Name: Humana, New York, NY

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