Design of robust and error-free signal-amplification circuit with orthogonal artificial nucleic acids

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H03933
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 37:Biomolecular chemistry and related fields
• Research Institution: Nagoya University
• Principal Investigator: Asanuma Hiroyuki 名古屋大学, 予防早期医療創成センター, 教授 (20282577)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: DNA / RNA / D-aTNA / Orthogonality / miRNA / Amplification circuit / SNA / fluorescent probe

Outline of Final Research Achievements

We have previously developed our original artificial nucleic acid, D-aTNA, which cross-pairs with neither natural D-DNA nor D-RNA. In contrast to D-aTNA, our SNA can cross-pair with D-aTNA, D-DNA, and D-RNA. With these artificial nucleic acids, a new signal amplification system was designed by combining D-aTNA amplification circuit with SNA interface. The D-aTNA amplification circuit can be triggered by natural D-RNA that is orthogonal to D-aTNA because interface SNA can convert input D-RNA into D-aTNA output. By using this system, we have successfully developed robust signal amplification system that can detect small amount of microRNA (miR21) in the presence of contaminating DNA and RNA.

Free Research Field

核酸化学

Academic Significance and Societal Importance of the Research Achievements

本研究が実現したことで、細胞内で微量のRNAをロバストに検出可能な新たな蛍光プローブの設計が可能になり、miRNAを標的とした病理診断など診断薬の開発が期待できる。またこれまの核酸の直交性の概念は天然のDNAあるいはRNAの配列特異性のみに留まっていたが、人工核酸が加わったことで天然および人工核酸間での二重鎖形成能に基づく直交性へと、直交性の概念が大きく拡張された。