| Project/Area Number |
18K19572
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
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| Research Institution | Chiba University |
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Principal Investigator |
Kaneda Atsushi 千葉大学, 大学院医学研究院, 教授 (10313024)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
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| Keywords | 癌 / エピジェネティクス / 阻害剤 / PIポリアミド / エピゲノム / がん / 化合物合成 / ピロールイミダゾールポリアミド |
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| Outline of Final Research Achievements |
Taking advantage by utilizing small molecules that bind to DNA by sequence-specific manner, we develop middle molecule compounds that can rewrite the accumulated epigenomic aberrations or prevent their accumulations in targeted genomic regions. Pyrrole-imidazole (PI) polyamides are cell-permeable and intravenously injectable molecules with low toxicity that can bind to the minor groove of DNA by sequence-specific manner. Epigeneitic inhibitors are conjugated to PI polyamides, and delivered to the targeted genomic regions by sequence-specific manner when given to cultured cancer cells. We established PI polyamides conjugated with epigenetic inhibitors that altered epigenome at selected regions. We also identified critical aberrant epigenomic alterations that were seen in cancer e.g. gastric and prostate cancer and could be candidate regions targeted by these conjugates.
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| Academic Significance and Societal Importance of the Research Achievements |
エピゲノムとは細胞のゲノムの修飾物のことで、どの遺伝子を使いどの遺伝子を使わないか、つまりは細胞の運命や振舞いを決定する働きを持ち、その異常は癌の重要な原因の１つとなる。しかし現状のエピゲノム阻害剤は、癌の原因となっている異常修飾領域だけでなく、正常な細胞に存在する重要な修飾も含めてゲノム全体で作用してしまうことで副作用が問題となる。本研究は、特定の塩基配列を含む選択的なゲノム領域のみエピゲノム阻害剤が作用することを可能にする化合物開発に挑戦し、技術的に成功するとともに、次の発展を目指し胃癌・前立腺癌などで重要なエピゲノム異常を標的とする化合物開発へと進行している。
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