한빛사논문
Woo‑Ri Shin1†, Dae‑Young Park1†, Ji Hun Kim2†, Jin‑Pyo Lee1, Nguyen Quang Thai1, In‑Hwan Oh1, Simranjeet Singh Sekhon1, Wooil Choi3, Sung Yeon Kim4, Byung‑Kwan Cho2, Sun Chang Kim2, Jiho Min3*, Ji‑Young Ahn1* and Yang‑Hoon Kim1*
1School of Biological Sciences, Chungbuk National University, 1 Chungdae‑Ro, Seowon‑Gu, Cheongju 28644, Republic of Korea. 2Department of Biologi‑cal Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak‑ro, Yuseong‑gu, Daejeon 34141, Republic of Korea. 3Graduate School of Semiconductor and Chemical Engineering, Jeonbuk National University, Jeonju 54896, Republic of Korea. 4College of Pharmacy, Wonkwang University, Shinyoung‑dong 344‑2, Iksan, Jeonbuk 570‑749, Republic of Korea.
*Correspondence
†Woo-Ri Shin, Dae-Young Park, and Ji Hun Kim contributed equally.
Abstract
Background
Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, is a biomarker of hepatocellular carcinoma (HCC) progression. Aptamers specifically binding to target biomolecules have recently emerged as clinical disease diagnosis targets. Here, we describe 3D structure-based aptaprobe platforms for detecting GPC3, such as aptablotting, aptaprobe-based sandwich assay (ALISA), and aptaprobe-based imaging analysis.
Results
For preparing the aptaprobe–GPC3 platforms, we obtained 12 high affinity aptamer candidates (GPC3_1 to GPC3_12) that specifically bind to target GPC3 molecules. Structure-based molecular interactions identified distinct aptatopic residues responsible for binding to the paratopic nucleotide sequences (nt-paratope) of GPC3 aptaprobes. Sandwichable and overlapped aptaprobes were selected through structural analysis. The aptaprobe specificity for using in HCC diagnostics were verified through Aptablotting and ALISA. Moreover, aptaprobe-based imaging showed that the binding property of GPC3_3 and their GPC3 specificity were maintained in HCC xenograft models, which may indicate a new HCC imaging diagnosis.
Conclusion
Aptaprobe has the potential to be used as an affinity reagent to detect the target in vivo and in vitro diagnosing system.
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