Development of clinical-fit aptamer targeting CYP24A1 using an integrated approach of high-speed atomic force microscopy and molecular docking

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15239
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47020:Pharmaceutical analytical chemistry and physicochemistry-related
• 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)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: CYP24 / Vitamin D3 / Aptamer / in vivo / A549 cells

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.

Free Research Field

Life Sciences

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.