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.
Highlights
MicroRNAs are a type of non-coding RNA that induce the post-transcriptional gene silencing of their target genes and regulate a wide range of biological processes, including apoptosis, differentiation, metabolism, and cell proliferation [1,2]
We determined whether the anti-exosome antibody could be introduced into the recipient cells
As antigens of anti-exosome antibody, CD9, CD63 and CD81, which are known as surface markers of exosomes, were selected [20]
Summary
MicroRNAs (miRNAs) are a type of non-coding RNA that induce the post-transcriptional gene silencing of their target genes and regulate a wide range of biological processes, including apoptosis, differentiation, metabolism, and cell proliferation [1,2]. Recent studies have reported that the aberrant expression of miRNAs is associated with many pathological disease processes [3,4,5]. Exosomal RNAs can be taken up by neighboring or distant recipient cells [7]. It has been reported that such miRNAs (exosomal miRNAs) regulate gene expression in the recipient cells [5,8,9,10]. Exosomal miRNAs can be considered as significant targets for cancer therapy [8,9,10]
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