2021 Fiscal Year Final Research Report
Elucidation of the mechanism for auto-penetrating DNA aptamers and their application as post-antibody drugs
Project/Area Number |
19H03512
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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Research Institution | Niigata University |
Principal Investigator |
Chuman Yoshiro 新潟大学, 自然科学系, 研究教授 (40372263)
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Co-Investigator(Kenkyū-buntansha) |
寺尾 豊 新潟大学, 医歯学系, 教授 (50397717)
東元 祐一郎 久留米大学, 医学部, 教授 (40352124)
阿部 貴志 新潟大学, 自然科学系, 教授 (30390628)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Keywords | 分子標的薬 / DNAアプタマー / がん / ホスファターゼ / 核酸医薬 |
Outline of Final Research Achievements |
Antibody drugs, which are broadly used in the application for anticancer therapy, are limited to extracellular targets due to their inability to penetrate cell membranes. We have focused on DNA aptamer molecules formed by single-stranded nucleic acids with antibody-like functions, and succeeded in developing a stimulus-responsive DNA molecule, "IRDAptamer which forms a cube-shaped structure upon ionic stimulation and shows high affinity and selectivity for an oncogenic protein. Furthermore, we identified the optimal sequence of the molecule based on structure-activity relationship studies. In addition, the functional analysis under the physiological conditions and studies in living mice suggested that this molecule could be developed as a post-antibody drug targeting intracellular oncogenic proteins.
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Free Research Field |
腫瘍診断および治療学関連
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Academic Significance and Societal Importance of the Research Achievements |
本研究では,既存の抗体薬やアプタマー薬の課題であった細胞内疾患関連タンパク質を標的に適応できないという課題克服を目指し,細胞内がん原因タンパク質を標的とした膜透過性イオン応答性DNAアプタマー(IRDAptamer)の開発に成功した.また,本分子の細胞膜透過メカニズム,ならびに必須配列を同定し,IRDAptamerの細胞内標的に対する有用性を確認した. ライブラリとして構築されたIRDAptamerは,多様な疾患に対して適用できる可能性を有していることから,細胞内を標的可能な新規創薬モダリティとして幅広い応用や社会的波及効果が期待できる.
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