Examination of oligonucleotide therapeutics based on the triplex DNA formation by artificial oligonucleotide

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H05100
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Drug development chemistry
• Research Institution: Kyushu University
• Principal Investigator: Taniguchi Yosuke 九州大学, 薬学研究院, 准教授 (00452714)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 創薬化学 / 核酸医薬 / ゲノム創薬 / アンチジーン核酸 / 核送達技術

Outline of Final Research Achievements

In this project, we aimed to create the antigene method, which is an oligonucleotide therapeutic that acts directly on abnormal genes and specifically inhibits their expression. We succeeded in the chemical synthesis of an artificial nucleic acid capable of binding to a gene region that can not be bound by natural nucleic acid, and revealed that stable and selective triplex DNA formation can be formed. Furthermore, we also succeeded in developing a new nuclear delivery technology, and succeeded in effectively inhibiting gene expression by antigene oligonucleotides having the artificial nucleic acid.

Free Research Field

核酸化学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、新規モダリティ創薬の一つとして期待される核酸医薬のなかでも、これまでに標的をされていない2本鎖DNAを標的とした新規創薬手法の基礎的成果を挙げているため、社会的な意義は大きい。また、核酸の高次構造の一つである3本鎖DNA形成を人工的に形成させることに着目した人工核酸の化学合成にも成功している。しかも、本研究で得られた人工核酸搭載アンチジーン核酸は、異常遺伝子を発現上流部である転写の段階を阻害する成果を挙げており、学術的な意義も非常に大きい。