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基于多价适配体结构介导的荧光适配体传感器,通过与杂交链式反应(HCR)和CRISPR-Cas系统偶联用于阿尔茨海默病的早期诊断

Polyvalent Aptamers Structure-Mediated Fluorescent Aptasensor for the Early Diagnosis of Alzheimer's Disease by Coupling with HCR and CRISPR-Cas System.

作者信息

Li Xinyi, Chen Bingjie, Xie Yaoyao, Luo Yi, Zhu Dan, Wang Lianhui, Su Shao

机构信息

State Key Laboratory of Organic Electronics and Information Displays & Jiangsu Key Laboratory of Smart Biomaterials and Theranostic Technology, Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, 9 Wenyuan Road, Nanjing 210023, China.

出版信息

Anal Chem. 2025 Jan 14;97(1):793-798. doi: 10.1021/acs.analchem.4c05329. Epub 2024 Dec 19.

DOI:10.1021/acs.analchem.4c05329
PMID:39700052
Abstract

The early diagnosis of Alzheimer's disease (AD) plays a vital role in slowing the progression of AD and improving the quality of human life. However, it is still a challenge in the medical field. Herein, an ultrasensitive fluorescent aptasensor was designed for the detection of special phosphorylated tau181 (P-tau181) by coupling with polyvalent aptamers (PAs) structure, hybridization chain reaction (HCR), and the CRISPR-Cas system. Coupling with the signal amplification strategy, the specific recognition ability of the aptamer, and the high cleavage activity of Cas12a protein, the designed aptasensor showed a wide linear range (0.1-10 pg/mL), a low detection limit (0.069 pg/mL), high selectivity, and excellent anti-interference ability for the detection of P-tau181. Moreover, the aptasensor can efficiently analyze P-tau181 in artificial cerebro spinal fluid (aCSF) and serum, proving that it has a promising application in the early diagnosis of AD.

摘要

阿尔茨海默病(AD)的早期诊断对于减缓AD的进展和提高人类生活质量起着至关重要的作用。然而,这在医学领域仍然是一项挑战。在此,通过与多价适体(PAs)结构、杂交链式反应(HCR)和CRISPR-Cas系统相结合,设计了一种超灵敏荧光适体传感器,用于检测特殊的磷酸化tau181(P-tau181)。结合信号放大策略、适体的特异性识别能力和Cas12a蛋白的高切割活性,所设计的适体传感器在检测P-tau181时表现出宽线性范围(0.1-10 pg/mL)、低检测限(0.069 pg/mL)、高选择性和出色的抗干扰能力。此外,该适体传感器能够有效分析人工脑脊液(aCSF)和血清中的P-tau181,证明其在AD早期诊断中具有广阔的应用前景。

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引用本文的文献

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Nucleic Acids Res. 2025 Jun 20;53(12). doi: 10.1093/nar/gkaf596.
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Research Progress on Signal Conversion Based on Aptamer Combined CRISPR/Cas System in Biosensors.基于适配体联合CRISPR/Cas系统的生物传感器信号转换研究进展
Mol Diagn Ther. 2025 Jun 18. doi: 10.1007/s40291-025-00785-7.