Development of Antibody-Oligonucleotide Complexes for Targeting Exosomal MicroRNA

针对外泌体微小RNA的抗体-寡核苷酸复合物的开发

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作者:Asako Yamayoshi, Shota Oyama, Yusuke Kishimoto, Ryo Konishi, Tsuyoshi Yamamoto, Akio Kobori, Hiroshi Harada, Eishi Ashihara, Hiroshi Sugiyama, Akira Murakami

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.

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