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In vitro optimization of 2 '-OMe-4 '-thioribonucleoside-modified anti-microRNA oligonucleotides and its targeting delivery to mouse liver using a liposomal nanoparticle
| Title: | In vitro optimization of 2 '-OMe-4 '-thioribonucleoside-modified anti-microRNA oligonucleotides and its targeting delivery to mouse liver using a liposomal nanoparticle |
| Authors: | Takahashi, Mayumi Browse this author | | Yamada, Naoki Browse this author | | Hatakeyama, Hiroto Browse this author →KAKEN DB | | Murata, Manami Browse this author | | Sato, Yusuke Browse this author | | Minakawa, Noriaki Browse this author | | Harashima, Hideyoshi Browse this author →KAKEN DB | | Matsuda, Akira Browse this author →KAKEN DB |
| Issue Date: | Dec-2013 |
| Publisher: | Oxford univ press |
| Journal Title: | Nucleic acids research |
| Volume: | 41 |
| Issue: | 22 |
| Start Page: | 10659 |
| End Page: | 10667 |
| Publisher DOI: | 10.1093/nar/gkt823 |
| PMID: | 24030710 |
| Abstract: | MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression post-transcriptionally. Previous studies, which characterized miRNA function, revealed their involvement in fundamental biological processes. Importantly, miRNA expression is deregulated in many human diseases. Specific inhibition of miRNAs using chemically modified anti-miRNA oligonucleotides (AMOs) can be a potential therapeutic strategy for diseases in which a specific miRNA is overexpressed. 2'-O-Methyl (2'-OMe)-4'-thioRNA is a hybrid type of chemically modified oligonucleotide, exhibiting high binding affinity to complementary RNAs and high resistance to nuclease degradation. Here, we evaluate 2'-OMe-4'-thioribonucleosides for chemical modification on AMOs. Optimization of the modification pattern using a variety of chemically modified AMOs that are perfectly complementary to mature miR-21 revealed that the uniformly 2'-OMe-4'-thioribonucleoside modified AMO was most potent. Further investigation showed that phosphorothioate modification contributed to long-term miR-122 inhibition by the 2'-OMe-4'-thioribonucleoside-modified AMO. Moreover, systemically administrated AMOs to mouse using a liposomal delivery system, YSK05-MEND, showed delivery to the liver and efficient inhibition of miR-122 activity at a low dose in vivo. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/54780 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 松田 彰
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