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Oncolytic Hairpin DNA Pair: Selective Cytotoxic Inducer through MicroRNA-Triggered DNA Self-Assembly

  • Kunihiko Morihiro*
    Kunihiko Morihiro
    Department of Chemistry and Biotechnology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8656, Japan
    *Email: [email protected]
  • Hiraki Osumi
    Hiraki Osumi
    Department of Chemistry and Biotechnology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8656, Japan
    More by Hiraki Osumi
  • Shunto Morita
    Shunto Morita
    Department of Chemistry and Biotechnology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8656, Japan
  • Takara Hattori
    Takara Hattori
    Department of Chemistry and Biotechnology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8656, Japan
  • Manami Baba
    Manami Baba
    Department of Chemistry and Biotechnology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8656, Japan
    More by Manami Baba
  • Naoki Harada
    Naoki Harada
    Department of Chemistry and Biotechnology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8656, Japan
    More by Naoki Harada
  • Riuko Ohashi
    Riuko Ohashi
    Histopathology Core Facility, Faculty of Medicine, Niigata University, Niigata 951-8510, Japan
    Division of Molecular and Diagnostic Pathology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata 951-8510, Japan
    More by Riuko Ohashi
  • , and 
  • Akimitsu Okamoto*
    Akimitsu Okamoto
    Department of Chemistry and Biotechnology, The University of Tokyo, Bunkyo-ku, Tokyo 113-8656, Japan
    *Email: [email protected]
Cite this: J. Am. Chem. Soc. 2023, 145, 1, 135–142
Publication Date (Web):December 20, 2022
https://doi.org/10.1021/jacs.2c08974
Copyright © 2022 American Chemical Society

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    Abstract

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    Artificial nucleic acids have attracted much attention as potential cancer immunotherapeutic materials because they are recognized by a variety of extracellular and intracellular nucleic acid sensors and can stimulate innate immune responses. However, their low selectivity for cancer cells causes severe systemic immunotoxicity, making it difficult to use artificial nucleic acid molecules for immune cancer therapy. To address this challenge, we herein introduce a hairpin DNA assembly technology that enables cancer-selective immune activation to induce cytotoxicity. The designed artificial DNA hairpins assemble into long nicked double-stranded DNA triggered by intracellular microRNA-21 (miR-21), which is overexpressed in various types of cancer cells. We found that the products from the hairpin DNA assembly selectively kill miR-21-abundant cancer cells in vitro and in vivo based on innate immune activation. Our approach is the first to allow selective oncolysis derived from intracellular DNA self-assembly, providing a powerful therapeutic modality to treat cancer.

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jacs.2c08974.

    • Additional experimental details, oligonucleotide sequences used, and figures, including photographs of mice (PDF)

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    Cited By

    This article is cited by 2 publications.

    1. Kunihiko Morihiro, Shunto Morita, Naoki Harada, Manami Baba, Jongmin Yum, Mitsuru Naito, Kanjiro Miyata, Genta Nagae, Akimitsu Okamoto. RNA Oncological Therapeutics: Intracellular Hairpin RNA Assembly Enables MicroRNA-Triggered Anticancer Functionality. Journal of the American Chemical Society 2024, 146 (2) , 1346-1355. https://doi.org/10.1021/jacs.3c09524
    2. Xiaoqi Ou, Zhengli Wan, Ying Xiong, Ke Huang, Zeliang Wei, Zulimire Nuermaimaiti, Yanting Chen, Duerdanna Yiliya, Hongyin Lin, Zhenjie Dai, Yi Li, Piaopiao Chen. Homogeneous Dual Fluorescence Count of CD4 in Clinical HIV-Positive Samples via Parallel Catalytic Hairpin Assembly and Multiple Recognitions. ACS Applied Materials & Interfaces 2023, 15 (32) , 38285-38293. https://doi.org/10.1021/acsami.3c06742

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