Development of innovative clinical analytical methods for next-generation drugs using DNA aptamers as molecular recognition elements

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08200
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Physical pharmacy
• Research Institution: University of Shizuoka
• Principal Investigator: Todoroki Kenichiro 静岡県立大学, 薬学部, 教授 (70341451)
• Co-Investigator(Kenkyū-buntansha): 林 秀樹 岐阜薬科大学, 薬学部, 准教授 (00419665)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 抗体医薬 / DNAアプタマー / バイオアナリシス

Outline of Final Research Achievements

In this study, we developed simple and accurate bioanalytical methods for various therapeutic monoclonal antibodies (mAbs) using a nucleic acid molecule with a special three-dimensional structure called DNA aptamer as a molecular recognition element. Specifically, various DNA aptamers that selectively bind to therapeutic mAbs, such as the anticancer drug bevacizumab and pertuzumab, were obtained, and using them, the ELAA method, a multi-sample simultaneous analysis method, and the aptamer affinity purification - high temperature reversed-phase LC method, a high-precision HPLC analysis method, were developed. These methods are superior to conventional analytical methods in terms of simplicity and accuracy, and it has been verified that they are useful as clinical analytical methods.

Free Research Field

分析化学

Academic Significance and Societal Importance of the Research Achievements

近年、抗体の機能を利用した抗体医薬ががんや関節リウマチの治療など汎用されているが、抗体医薬の効き目を正しく評価し、適切な治療へとつなげるためには、血中の抗体医薬濃度を正確に測定する必要がある。しかし、血中には抗体医薬と構造の非常によく似た抗体が数多く存在するため、その分析は容易ではなかった。我々はDNAアプタマーと呼ばれる特殊な立体構造を持つ核酸分子を分子認識素子として用い、種々の抗体医薬に対する簡便かつ正確な血中濃度分析法を開発しました。我々の分析法は、新薬やバイオシミラー開発期間の効率化、迅速な薬物治療効果判定や薬物投与計画策定などへの貢献が期待できる。