Development of anti-miRNA oligonucleotides with stable duplexes to control cardiac diseases.
| Project/Area Number |
25293030
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | National Institute of Advanced Industrial Science and Technology |
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Principal Investigator |
Komatsu Yasuo 国立研究開発法人産業技術総合研究所, 生物プロセス研究部門, 研究グループ長 (30271670)
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| Co-Investigator(Kenkyū-buntansha) |
南川 典昭 徳島大学, 大学院医歯薬学研究部, 教授 (40209820)
平野 悠 国立研究開発法人産業技術総合研究所, 生物プロセス研究部門, 主任研究員 (70415735)
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2015: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
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| Keywords | microRNA / アンチセンス / 核酸医薬 / RNA / クロスリンク / オリゴヌクレオチド / miRNA / siRNA / 核酸 |
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| Outline of Final Research Achievements |
We had previously developed an interstrand cross-link (CL) that covalently conjugates a pair of apurinuc/apyrimidinic sites (AP sites) on complementary DNA duplex. We first examined whether the AP site-based cross-link could be applied to complementary 2′-O-methyl RNA (MeRNA) duplexes. Next, we prepared several MeRNA-based anti-miRNA oligonucleotides (AMOs) having CL duplex at the end(s) of the antisense strand, and investigated relationship between the miRNA inhibition activity and the AMO structure. Interestingly, the AMO having the CL-duplex at both terminals exhibited the highest activity and the inhibitory activity was largely affected by the positions of the duplex in AMO molecules. These results indicate the potency of the present structural basis for developing AMO as therapeutic applications.
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Report
(5 results)
Research Products
(35 results)
