Development of Novel Drug Delivery System Targeting Exosomal microRNA

Asako Yamayoshi
2020 Yakugaku zasshi  
Recently, mRNAs and microRNAs (miRNAs) have been identified in exosomes, which can be taken up by neighboring or distant cells. These exosomal-miRNAs may regulate gene expression in recipient cells. miRNAs are a type of non-coding RNA that induce post-transcriptional gene silencing of their target genes and regulate a wide range of biological processes, including apoptosis, differentiation, metabolism, and cell proliferation. According to recent reports, aberrant expression of miRNAs is
more » ... f miRNAs is associated with most pathological disease processes, including carcinogenesis. Therefore circulating onco-miRs are considered as significant therapeutic targets for cancer therapy. However, there is no report to regulate the function of miRNAs in exosomes. In this study, we developed novel drug delivery system using anti-exosome antibody-oligonucleotide conjugates (ExomiR-Tracker) for functional inhibition of circulating miRNAs. The "ExomiR-Tracker" is the world's first innovative molecule that has targeting property for exosome-recipient cells and specifically delivers nucleic acid medicines to the target cells. We found that ExomiR-Tracker can bind to the surface of exosomes and that the complexes are introduced into exosome-recipient cells then inhibit the activity of miRNA. We showed that ExomiR-Tracker can accumulate in cancerous tumors after intravenous administration. Existing technologies have difficulties for introducing anti-miR into exosomes and extremely low possibility to deliver anti-miR to exosome-recipient cells after intravenous administration. However, we successfully developed useful inhibition technology against exosomal-miRNA.
doi:10.1248/yakushi.19-00218-3 pmid:32378662 fatcat:bwleof4zozditmg6pl5tpe5s5y