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Delivery of Nucleic Acid Drugs

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Nucleic Acid Drugs

Part of the book series: Advances in Polymer Science ((POLYMER,volume 249))

Abstract

Nucleic acid drugs should be delivered into the corresponding intracellular target site, i.e. the nucleus or cytosol. Because biosystems have developed several barriers to prevent the intrusion of external genetic material, highly sophisticated delivery machinery must be used to overcome those barriers. In this review, we describe the evolution of polymer-based carriers over several decades of research. To prevent deactivation in extracellular circumstances, nucleic acid drugs are condensed with cationic polymers or encapsulated with hydrophobic polymers. The condensed or encapsulated complexes are often crosslinked to enhance the physicochemical stability and coated with biocompatible polymers for safety. Delivery of the nucleic acid drugs to a specific site and subsequent intracellular entry can be partially accomplished by passive targeting based on the enhanced permeability and retention (EPR) effect or nonspecific endocytosis, but more effectively by receptor-mediated endocytosis. After the cell entry, various functionalities help the nucleic acid drugs escape the endosomes to enter the cytosol, release them from the carrier system, and transfer them into nucleoplasm through the nuclear envelope. The development of an ideal delivery carrier with efficiency, specificity, as well as safety has been supported by progress in polymer chemistry and supramolecular chemistry, and accumulated experience in biological and clinical trials.

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Acknowledgements

This work was supported by Research Settlement Fund for the new faculty of Seoul National University (SNU) and a Core Research for Evolutional Science and Technology (CREST) grant from the Japan Science and Technology Agency (JST).

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Authors and Affiliations

  1. Department of Chemistry, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul, 151-747, Korea

    Yan Lee

  2. Center for Nanobio Integration, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan

    Kazunori Kataoka

  3. Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Kazunori Kataoka

  4. Department of Materials Engineering, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan

    Kazunori Kataoka

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  1. Yan Lee
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  2. Kazunori Kataoka
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Correspondence to Kazunori Kataoka .

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Editors and Affiliations

  1. Dept. Biomolecular Engineering, Kyoto Institute of Technology, Matsugasaki, Kyoto, 606-8585, Japan

    Akira Murakami

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Lee, Y., Kataoka, K. (2011). Delivery of Nucleic Acid Drugs. In: Murakami, A. (eds) Nucleic Acid Drugs. Advances in Polymer Science, vol 249. Springer, Berlin, Heidelberg. https://doi.org/10.1007/12_2011_129

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