2015 Fiscal Year Final Research Report
Drug discovery driven by structural plasticity of RNA
| Project/Area Number |
24241074
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical biology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2012-10-31 – 2016-03-31
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| Keywords | アプタマー / SELEX / 核酸医薬 / 創薬標的 / アンタゴニスト / アゴニスト / RNA造形力 / 構造生物学 |
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| Outline of Final Research Achievements |
Aptamer is a folded single-stranded nucleic acid that binds given molecules. The concept is based on the ability of short (20-80 mer) sequences to fold, in the presence of a target, into unique three-dimensional structures, which allow the aptamer to bind target molecules with high affinity and specificity. In this study, we developed several RNA and/or DNA aptamers by SELEX method to therapeutic target proteins such as Midkine, Autotaxin and FGF2. The therapeutic potency of these aptamers for cancer, fibrosis and bone diseases, respectively, was confirmed in the in vitro (cell-based) and in vivo (animal-based) studies. In collaboration with O. Nureki’s group of The University of Tokyo, we solved the crystal structure of Autotaxin complexed with the aptamer at the 2.0 angstrom resolution, uncovering the inhibitory mechanism and the structure-function relationship.
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| Free Research Field |
RNA医科学
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