2023 Fiscal Year Final Research Report
Multiplex SELEX-based selection strategy to generate multifunctional aptamers targeting the transferrin receptor (TfR) and the insulin receptor (IR).
Project/Area Number |
22K14789
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
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Research Institution | The University of Tokyo |
Principal Investigator |
Amano Ryo 東京大学, 医科学研究所, 特任研究員 (20818687)
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Project Period (FY) |
2022-04-01 – 2024-03-31
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Keywords | Multiplex SELEX法 / RNAアプタマー / 核酸医薬 / 脳内薬剤送達(DDS) / インスリン受容体(IR) / トランスフェリン受容体(TfR) / マルチプレックス化 / 表面プラズモン共鳴(SPR)法 |
Outline of Final Research Achievements |
In this study, we generated RNA aptamers that bind to the transferrin receptor (TfR) or the insulin receptor (IR), known targets for drug delivery to the brain. To identify aptamers that are cross-reactive with the mouse and human receptors and do not block the interaction of the target receptor with the ligand, we established an advanced multiplex SELEX method using two or more different target molecules such as the mouse and human receptors in ligand-bound and ligand-unbound forms. After selection and high-throughput sequencing, surface plasmon resonance-based analyses revealed that some aptamers can bind to mouse and human receptors and hardly compete for the interaction between the target receptor and the ligand. This result suggests that our selection method has the potential to identify molecules with diverse functions by changing the type and combination of targets and may be valuable in drug discovery studies.
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Free Research Field |
RNA工学
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Academic Significance and Societal Importance of the Research Achievements |
創薬シーズの探索技術の強化・高度化は、あらゆる疾患や生命現象の制御(創薬)と理解の深化(学術)に必須である。本課題で構築した複数の標的分子を組合せた高度マルチプレックス化によって標的部位を限定化する技術は、選抜材料の種類や組合せを変更することで高い汎用性を発揮し、ニーズの高い創製技術基盤へと発展することが期待できる。また、脳内薬剤送達の標的分子のTfRおよびIRをモデル標的としたため、本課題で創製したアプタマーは、ニーズが高まり続ける神経疾患の治療薬開発研究に貢献する具体的成果物として期待できる。
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