2022 Fiscal Year Annual Research Report
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 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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| Keywords | CYP24 / Aptamer / Vitamin D3 |
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| Outline of Annual Research Achievements |
Vitamin D3 is metabolized to 1α, 25-dihydroxy vitamin D3 (1,25D3), which exerts various physiological effects such as bone formation, cell proliferation, and differentiation. Thus, 1,25D3 and its analogs have been clinically used as therapeutic agents against rickets and psoriasis, furthermore, they have been also expected as cancer treatments. CYP24A1 (CYP24) is a key enzyme that catalytically degrades the 1,25-D3, thus overexpression of CYP24 leads the various types of diseases such as osteoporosis and cancer. 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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[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
Open Access / Int'l Joint Research
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