| Project/Area Number |
26670055
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Drug development chemistry
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
SUGIYAMA Hiroshi 京都大学, 理学研究科, 教授 (50183843)
BANDO Toshikazu 京都大学, 理学研究科, 准教授 (20345284)
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| Project Period (FY) |
2014-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
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| Keywords | 天然分子を模倣した化合物 / DNAベースの治療 / 遺伝子発現制御 / マルチターゲットな小分子化合物 / エピゲノム |
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| Outline of Final Research Achievements |
Synthetic transcriptional activators adept of therapeutic gene modulation could be harnessed for developing strategies to treat some uncured defect-transcriptional machinery associated disorders. We have successfully advanced distinct DNA-based epigenome-modulating small molecules as first-ever bio-inspired genetic switches for activating exclusive cluster of therapeutically important genes including those providing resistance towards ocular disorders and HIV. Also, an `ON` switch for miR-302 familial microRNAs and an `OFF` switch for EVI1 oncogene were developed. Integration of epigenetic modulators on synthetic DNA-based domain effectively activated genes associated pluripotency and cartilage development. Next-generation sequencing studies guided the construction of second-generation genetic switches. Our proof-of-concept studies validate the switchable roles of epigenetic enzymes in gene regulation and provide a molecular basis for developing versatile bioactive ligands.
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