Development of Antibody–Oligonucleotide Complexes for Targeting Exosomal MicroRNA
Asako Yamayoshi,
Shota Oyama,
Yusuke Kishimoto,
Ryo Konishi,
Tsuyoshi Yamamoto,
Akio Kobori,
Hiroshi Harada,
Eishi Ashihara,
Hiroshi Sugiyama,
Akira Murakami
Affiliations
Asako Yamayoshi
Chemistry of Functional Molecules, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki-shi, Nagasaki 852-8521, Japan
Shota Oyama
Chemistry of Functional Molecules, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki-shi, Nagasaki 852-8521, Japan
Yusuke Kishimoto
Faculty of Molecular Chemistry and Engineering, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan
Ryo Konishi
Faculty of Molecular Chemistry and Engineering, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan
Tsuyoshi Yamamoto
Chemistry of Functional Molecules, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki-shi, Nagasaki 852-8521, Japan
Akio Kobori
Faculty of Molecular Chemistry and Engineering, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan
Hiroshi Harada
Laboratory of Cancer Cell Biology, Graduate School of Biostudies, Kyoto University, Yoshida-Konoecho, Sakyo-ku, Kyoto 606-8501, Japan
Eishi Ashihara
Department of Clinical and Translational Physiology, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan
Hiroshi Sugiyama
Department of Chemistry, Graduate School of Science, Kyoto University, Kitashirakawa-Oiwakecho, Sakyo-ku, Kyoto 606-8502, Japan
Akira Murakami
Faculty of Molecular Chemistry and Engineering, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan
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.
