Amino acid substitution without genetic modification

• Project/Area Number: 15H05491
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Bio-related chemistry
• Research Institution: Nagoya University
• Principal Investigator: Hagihara Shinya 名古屋大学, 理学研究科, 准教授 (80373348)
• Research Collaborator: YAMASHITA Shun
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥24,310,000 (Direct Cost: ¥18,700,000、Indirect Cost: ¥5,610,000); Fiscal Year 2017: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000); Fiscal Year 2016: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000); Fiscal Year 2015: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
• Keywords: 革新的遺伝子治療 / 核酸医薬 / アンチセンス / ナンセンス変異 / リードスルー / 核酸 / 糖 / リボソーム結合分子 / 生体分子 / 遺伝情報変換

Outline of Final Research Achievements

A nonsense mutation is a genetic mutation that converts a codon coding an amino acid to the stop codon called premature termination codon (PTC). This mutation causes a variety of diseases including Duchenne muscular dystrophy and cystic fibrosis. One of the potential methods for treating such diseases is readthrough therapy that is accomplished by the incorporation of an amino acid to PTC during translation and hence produces the full-length proteins. So far, aminoglycosides and other synthetic compounds that reduce the translation fidelity have been utilized to readthrough therapy. However, their toxicity due to the non-specific induction of inaccurate translation hampered their clinical use. In this study, we have developed a novel readthrough strategy that enables the target PTC-specific readthrough.

Research Products

• [Int'l Joint Research] University of Munster(Germany)
• [Journal Article] Key Structural Elements of Unsymmetrical Cyanine Dyes for Highly Sensitive Fluorescence Turn-On DNA Probes (2017)
  • Author(s): Uno K., Sasaki T., Sugimoto N., Ito H., Nishihara T., Hagihara S., Higashiyama T., Sasaki N., Sato Y., Itami K.
  • Journal Title: Chemistry, an Asian Journal Volume: 12 Pages: 233-238
  • DOI: 10.1002/asia.201601430
  • Peer Reviewed / Open Access
• [Journal Article] High-throughput Assay for Quantification of Aminoglycoside–Ribosome Interaction (2016)
  • Author(s): Shun Yamashita, Dominik Bergmann, Ayato Sato, Mika Nomoto, Yasuomi Tada, Hans-Ulrich Humpf, Kenichiro Itami and Shinya Hagihara
  • Journal Title: Chem. Lett. Volume: 45 Issue: 9 Pages: 1048-1050
  • DOI: 10.1246/cl.160508
  • NAID: 130005549100
  • ISSN: 0366-7022, 1348-0715
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Probing strigolactone receptors in Striga hermonthica with fluorescence. (2015)
  • Author(s): Tsuchiya, Y., Yoshimura, M., Sato, Y., Kuwata, K., Toh, S., Holbrook-Smith, D., Zhang, H., McCourt, P., Itami, K., Kinoshita, T. and Hagihara, S.
  • Journal Title: Science Volume: 349 Pages: 864-868
  • DOI: 10.1126/science.aab3831
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Sequence-specific Readthrough of Termination Codon by Antisense Oligonucleotides (2018)
  • Author(s): YAMASHITA, Shun; ITAMI, Kenichiro; HAGIHARA, Shinya
  • Organizer: 日本化学会第98春季年会
• [Presentation] 新規リボソーム結合性分子の 迅速スクリーニング (2017)
  • Author(s): 山下 隼・佐藤 綾人・伊丹 健一郎・萩原 伸也
  • Organizer: 日本化学会第97春季年会
  • Place of Presentation: 慶応大学
  • Year and Date: 2017-03-16
• [Presentation] High throughput screening for the novel translation regulator (2017)
  • Author(s): Shun Yamashita, Ayato Sato, Kenichiro Itami, Shinya Hagihara
  • Organizer: グリーン自然科学国際教育研究プログラム IGER 2016年度年次報告会
  • Place of Presentation: 名古屋大学
• [Presentation] 新規リボソーム結合性分子の探索 (2015)
  • Author(s): 山下隼・萩原伸也・佐藤綾人・野元美佳・多田安臣・伊丹健一郎
  • Organizer: 第9回バイオ関連化学シンポジウム
  • Place of Presentation: 熊本
  • Year and Date: 2015-09-10
• [Presentation] 新規翻訳制御分子の探索に向けたスクリーニング法の開発 (2015)
  • Author(s): 山下隼・佐藤綾人・野元美佳・多田安臣・伊丹健一郎・萩原伸也
  • Organizer: 第3回バイオ関連化学シンポジウム若手フォーラム
  • Place of Presentation: 熊本
  • Year and Date: 2015-09-09