Engineering G-quadruplex aptamer to modulate its binding specificity

作     者：Long Li Shujuan Xu Xueyu Peng Yuzhuo Ji He Yan Cheng Cui Xiaowei Li Xiaoshu Pan Lu Yang Liping Qiu Jianhui Jiang Weihong Tan Long Li;Shujuan Xu;Xueyu Peng;Yuzhuo Ji;He Yan;Cheng Cui;Xiaowei Li;Xiaoshu Pan;Lu Yang;Liping Qiu;Jianhui Jiang;Weihong Tan

作者机构：Department of Chemistry and Department of Physiology and Functional GenomicsCenter for Research at the Bio/Nano Interface Health Cancer Center UF Genetics InstituteMcKnight Brain Institute University of Florida Molecular Science and Biomedicine Laboratory State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical Engineering College of Biology Aptamer Engineering Center of Hunan ProvinceHunan University Molecular Science and Biomedicine Laboratory(MBL)State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical Engineering College of Biology Aptamer Engineering Center of Hunan ProvinceHunan University Institute of Molecular Medicine(IMM) Renji HospitalShanghai Jiao Tong University School of Medicine and College of Chemistry and Chemical EngineeringShanghai Jiao Tong University 

出 版 物：《National Science Review》 (国家科学评论(英文版))

年 卷 期：2021年第8卷第4期

页      面：107-113页

核心收录：

学科分类：0831[工学-生物医学工程（可授工学、理学、医学学位）] 08[工学] 0836[工学-生物工程] 

基　　金：supported by the National Institutes of Health(GM079359 and CA133086) the Natural Science Foundation of China (21505032, 21325520 and 1327009) 

主　　题：G-quadruplex aptamer i-motif binding specificity cell microenvironment 

摘      要：The use of aptamers in bioanalytical and biomedical applications exploits their ability to recognize cell surface protein receptors. Targeted therapeutics and theranostics come to mind in this regard. However,protein receptors occur on both cancer and normal cells; as such, aptamers are now taxed with identifying high vs. low levels of protein expression. Inspired by the flexible template mechanism and elegant control of natural nucleic acid-based structures, we report an allosteric regulation strategy for constructing a structure-switching aptamer for enhanced target cell recognition by engineering aptamers with DNA intercalated motifs(i-motifs) responsive to the microenvironment, such as p H. Structure-switching sensitivity can be readily tuned by manipulating i-motif sequences. However, structure-switching sensitivity is difficult to estimate, making it equally difficult to effectively screen modified aptamers with the desired sensitivity. To address this problem, we selected a fluorescent probe capable of detecting G-quadruplex in complicated biological media.