| Project/Area Number |
22KF0089
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| Project/Area Number (Other) |
22F22024 (2022)
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Multi-year Fund (2023)
Single-year Grants (2022) |
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| Section | 外国 |
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| Review Section |
Basic Section 37020:Chemistry and chemical methodology of biomolecules-related
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| Research Institution | The University of Tokyo |
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Principal Investigator |
菅 裕明 東京大学, 大学院理学系研究科(理学部), 教授 (00361668)
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| Co-Investigator(Kenkyū-buntansha) |
COLAS KILIAN 東京大学, 大学院理学系研究科(理学部), 外国人特別研究員
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| Project Period (FY) |
2023-03-08 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2023: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2022: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | protein engineering / grafting / KRas / peptide / lasso-graft / macrocylic peptides / RaPID |
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| Outline of Research at the Start |
In fiscal year 2023, we will focus on addressing the drug delivery issue via viral vectors. By December 2023, we hope to have drug candidates ready for further clinical evaluation and a first proof-of-concept publication. Thereafter, further fine-tuning of the lead candidate, and development of new generation of compounds against other currently undruggable targets will be pursued.
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| Outline of Annual Research Achievements |
We have identified 20 lasso-grafted peptides, termed “Ubodies”, that target one of the major cancer-drivers, KRas(G12D). Some compounds bind to the protein target with high selectivity towards the cancer-driver “on” state of KRas vs its “off” state; while others are selective towards the mutant form vs its wildtype parent (some compounds exhibit dual selectivity). These Ubodies thus have high potential as therapeutic candidates with very little side-effects. Furthermore, we have also developed a new method to identify de novo highly potent Ubodies without the need for a previous binding peptide, which we are currently applying to other cancer targets. We have also started investigating drug delivery avenues (lipid nanoparticles & gene delivery), and early protocols are being validated.
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