2021 Fiscal Year Final Research Report
Development of multi-functional siRNA-aptamer chimera for virus infections
| Project/Area Number |
20K21880
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 90:Biomedical engineering and related fields
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2020-07-30 – 2022-03-31
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| Keywords | RNAアプタマー / siRNA / ウイルス / キメラ核酸 |
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| Outline of Final Research Achievements |
The aim of this study is to generate a new therapeutic agent for viral infection. To address this, we generated siRNA-aptamer chimera molecule multiply achieving viral neutralization and degradation of viral genome. In the study, we focused on a re-emerging virus disease, dengue virus (DENV), as model target, and generated aptamers and siRNA targeting DNEV E-protein and RNA viral genome, respectively. As a result, we succeeded in identifying aptamers with binding and neutralizing activity to DENV, and further succeeded in design of siRNAs degrading DENV genomic RNA sequences. After development of each functional molecule, chimeric nucleic acids were prepared, and their performance as a complex was evaluated by SPR analysis and reporter assay in vitro. A series of assays revealed that chimeric molecule retained both binding activities and RNA interference ability.
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| Free Research Field |
RNA医科学
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| Academic Significance and Societal Importance of the Research Achievements |
ウイルス感染症には、デングウイルスなどの未だ効果的なワクチンや中和抗体が開発できていない再興ウイルス感染症が多く存在する。長期にわたり続く課題の克服には、新たなアプローチによる治療薬開発への挑戦的研究が必要である。その実現のため我々は、上市実績のある機能性核酸「アプタマー」「siRNA」の２つを活用することで、ウイルス中和活性とウイルスゲノム分解活性を併せ持つ「多重特異性多機能キメラ核酸」の開発とその有効性評価を実施した。多様化が進む創薬モダリティの一つとしてキメラ核酸を提案し、その有効性を検証した本成果は今後のウイルス治療分子開発を議論する上で大きな意義を有していると考えられる。
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