| Project/Area Number |
21K15239
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
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| Research Institution | Kanazawa University |
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Principal Investigator |
Biyani Madhu 金沢大学, ナノ生命科学研究所, 特任助教 (30882245)
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| Project Period (FY) |
2021-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2021: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | CYP24 / Vitamin D3 / Aptamer / in vivo / A549 cells / HS-AFM / Molecular docking / CYP24A1 |
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| Outline of Research at the Start |
The overexpression of CYP24A1 in cancer cells decreases the level of vitamin D3, which has the anti-proliferative effect. We identified a highly specific CYP24A1 inhibiting DNA aptamer by in vitro methods. This project will optimize the aptamer using HS-AFM in combination with molecular docking to develop as the potent and specific CYP24A1-inhibitor for cancer therapeutics.
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| Outline of Final Research Achievements |
Aptamer Apt-7 has shown high binding affinity, specificity, and inhibitory potency against CYP24 as well as anti-proliferative ability in vitro and in cellular assays. Next, we evaluated Apt-7 by in vivo study. To enhance the nucleases resistance in vivo, we designed and developed a circular bivalent version of Apt-7, called Cb-7, and performed systematic studies of Cb-7. Cb-7 showed high nuclease stability with increased functional activity and remarkable anti-proliferative effects in lung cancer cell line A549 cells. As a preliminary test, we investigated Cb-7 in vivo. We established an evaluation system of a xenograft mouse model with A549 cells. 1,25D3 was administered intraperitoneally three times a week, while Cb-7 was administrated directly into the tumor three times a week only in the tumor of the left shoulder. As the result, the tumor volume of the left shoulder (with Cb-7) showed a tendency to decrease. However, further study is needed in the future.
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| Academic Significance and Societal Importance of the Research Achievements |
The novel aptamer identified in this study presents an opportunity to generate a new probe for the recognition and inhibition of CYP24 for biomedical research and could assist in the diagnosis and treatment of cancer.
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