Efficacy of microRNA silencing by lipid-conjugated double-stranded antisense oligonucleotides
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- Guo Huijia
- Department of Neurology and Neurological Science, Tokyo Medical and Dental University
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- Yoshioka Kotaro
- Department of Neurology and Neurological Science, Tokyo Medical and Dental University
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- Kunieda Taiki
- Department of Neurology and Neurological Science, Tokyo Medical and Dental University
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- Asami Yutaro
- Department of Neurology and Neurological Science, Tokyo Medical and Dental University
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- Miyata Haruka
- Department of Neurology and Neurological Science, Tokyo Medical and Dental University
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- Yoshida-Tanaka Kie
- Department of Neurology and Neurological Science, Tokyo Medical and Dental University
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- Nagata Tetsuya
- Department of Neurology and Neurological Science, Tokyo Medical and Dental University
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- Yokota Takanori
- Department of Neurology and Neurological Science, Tokyo Medical and Dental University
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抄録
MicroRNAs (miRNAs) are important therapeutic targets for intractable diseases and antisense oligonucleotides that silence microRNA (antagomirs) have been developed for clinical applications. Although conjugation of ligands to antagomirs is a promising means of delivering them to target tissues and cells, the efficacy of these constructs is yet to be optimized. In this study, we designed a novel antagomir construct that comprise an antagomir strand and its complementary RNA strand. We were then able to indirectly conjugate ligands to this double-stranded antagomir via the complementary RNA strand. We then used single- or doublestranded antagomirs to examine effects of ligand type, conjugation site, or chemical modifications of the antagomir strand on miRNA silencing in vitro. We found that indirect conjugation of cholesterol ligand to a double-stranded antagomir produced a construct with comparable miRNA-silencing efficacy as that of a single-stranded antagomir directly conjugated with the ligand. Our findings support application of this technology for the therapeutic regulation of miRNA.
収録刊行物
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- Journal of Medical and Dental Sciences
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Journal of Medical and Dental Sciences 65 (2), 83-88, 2018
国立大学法人 東京医科歯科大学
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詳細情報 詳細情報について
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- CRID
- 1390001288038372992
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- NII論文ID
- 130007410292
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- ISSN
- 21859132
- 13428810
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可