A basic and theoretical research for practical application of new AIDS treatment method by lethal mutagenesis

• Project/Area Number: 16K00389
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Life / Health / Medical informatics
• Research Institution: Toyohashi University of Technology
• Principal Investigator: Harada Koji 豊橋技術科学大学, 工学(系)研究科(研究院), 助教 (40390504)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: HIV-1 / エイズ / 代替療法 / 数理モデル / コンピュータシミュレーション / 変異原 / 生体生命情報学

Outline of Final Research Achievements

Currently, the development of a new AIDS treatment method called "lethal mutagenesis method" in which the HIV-1 gene is destroyed by mutagenesis by a mutagen is being promoted mainly in Europe and the United States. In this study, mainly two results were obtained from a mathematical approach, aiming at early practical application of the treatment method. First, the effectiveness of combined treatment of mutagens and existing anti-HIV-1 drugs (reverse transcriptase inhibitors) was confirmed by simulation experiments. The other revealed the mechanism of elimination of HIV-1 latently infected cells by this treatment. Specifically, we showed that latently infected cells gradually decreased under treatment with mutagens, and we succeeded in identifying the parameters that determine the rate of decrease.

Academic Significance and Societal Importance of the Research Achievements

・致死的突然変異生成法に基づく新規エイズ治療法を確立するための有用な知見や、臨床実験を成功させるための具体的指針（実施条件等）を得るための理論を構築することができる。
・多剤耐性HIV株の出現により既存薬による治療が困難なエイズ患者は今後益々増えてくると考えられる。そのような事態になる前に、新規のエイズ治療法を確立しておくことは大変重要であり、本研究で得られた知見を通して新規エイズ治療法研究の進度を加速化できる。

Research Products

• [Journal Article] A mathematical study on combination effects of an immune checkpoint inhibitor and a mutagen for anti-HIV-1 therapies (2020)
  • Author(s): Kouji Harada , Tomonari Sumi
  • Journal Title: PROCEEDINGS OF THE TWENTY FIFTH INTERNATIONAL SYMPOSIUM ON ARTIFICIAL LIFE AND ROBOTICS (AROB 25TH '20) Volume: - Pages: 125-129
  • Peer Reviewed
• [Journal Article] A mathematical study for the development of anti-HIV-1 therapies based on the lethal mutagenesis method (2020)
  • Author(s): Kouji Harada
  • Journal Title: Artificial Life and Robotics Volume: 25 Issue: 2 Pages: 273-277
  • DOI: 10.1007/s10015-019-00578-2
  • Peer Reviewed
• [Presentation] A mathematical study on combination effects of an immune checkpoint inhibitor and a mutagen for anti-HIV-1 therapies (2020)
  • Author(s): Kouji Harada , Tomonari Sumi
  • Organizer: THE TWENTY FIFTH INTERNATIONAL SYMPOSIUM ON ARTIFICIAL LIFE AND ROBOTICS (AROB 25TH '20)
  • Int'l Joint Research
• [Presentation] A mathematical study for the development of anti-HIV-1 therapies based on the lethal mutagenesis method (2019)
  • Author(s): Kouji Harada
  • Organizer: 24th International Symposium on Artificial Life and Robotics
  • Int'l Joint Research
• [Presentation] 致死的突然変異生成法によるエイズ治療の理論的考察 (2018)
  • Author(s): 原田耕治
  • Organizer: 日本物理学会2018秋季大会
• [Presentation] 致死的突然変異生成法によるHIV-1増殖抑制に関する検討 (2018)
  • Author(s): 原田耕治
  • Organizer: 日本物理学会第73回年次大会