Development of clinical-fit aptamer targeting CYP24A1 using an integrated approach of high-speed atomic force microscopy and molecular docking
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 |
Review Section |
Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
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Research Institution | Kanazawa University |
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 |
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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Report
(3 results)
Research Products
(7 results)
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[Journal Article] Highlights from the 24th workshop on vitamin D in Austin, September 20222023
Author(s)
Meyer Mark B.Biyani Madhu、Campbell Moray J.、Chaudhari Snehal N.、Christakos Sylvia、Ingles Sue A.、Knuth Megan M.、Lee Seong Min、Lisse Thomas S.、Liu Eva S.、Piec Isabelle、Plum Lori A.、Rao Sudhaker D.、Reynolds Carmen J.、Thacher Tom D.、White John H.、Cantorna Margherita T.
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Journal Title
The Journal of Steroid Biochemistry and Molecular Biology
Volume: 228
Pages: 106247-106247
DOI
Related Report
Open Access / Int'l Joint Research
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