Development of Antibody-Oligonucleotide Complexes for Targeting Exosomal MicroRNA

  • Pharmaceutics. 2020 Jun 12;12(6):545. doi: 10.3390/pharmaceutics12060545.
Asako Yamayoshi  1  2 Shota Oyama  1 Yusuke Kishimoto  3  4 Ryo Konishi  3  4 Tsuyoshi Yamamoto  1 Akio Kobori  3 Hiroshi Harada  5 Eishi Ashihara  6 Hiroshi Sugiyama  4 Akira Murakami  3
Affiliations
  • 1. Chemistry of Functional Molecules, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki-shi, Nagasaki 852-8521, Japan.
  • 2. PRESTO, Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
  • 3. Faculty of Molecular Chemistry and Engineering, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
  • 4. Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto 606-8502, Japan.
  • 5. Laboratory of Cancer Cell Biology, Graduate School of Biostudies, Kyoto University, Yoshida-Konoecho, Sakyo-ku, Kyoto 606-8501, Japan.
  • 6. Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
Abstract

MicroRNAs in exosomes (exosomal miRNAs) are considered as significant targets for Cancer therapy. Anti-miR oligonucleotides are often used for the functional inhibition of miRNAs; however, there are no studies regarding the regulation of exosomal miRNA functions. In this study, we attempted to develop a novel drug delivery system using anti-exosome antibody-anti-miR oligonucleotide complexes (ExomiR-Tracker) to hijack exosomes to carry anti-miR oligonucleotides inside exosome-recipient cells. We found that ExomiR-Tracker bound to the exosomes, and then the complexes were introduced into the recipient cells. We also found that anti-miR oligonucleotides introduced into the recipient cells can exhibit inhibitory effects on exosomal miRNA functions in vitro and in vivo. We believe that our strategy would be a promising one for targeting exosomal miRNAs.

Keywords
antibody; drug delivery system; exosome; microRNA; nucleic acid drug.
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