Signal-On Electrochemical Detection for Drug-Resistant Hepatitis B Virus Mutants through Three-Way Junction Transduction and Exonuclease III-Assisted Catalyzed Hairpin Assembly
- Jiaxue YuJiaxue YuKey Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education, National & Local United Engineering Laboratory for Power Batteries, Key Laboratory of Nanobiosensing and Nanobioanalysis at Universities of Jilin Province, Analysis and Testing Center, Department of Chemistry, Northeast Normal University, Changchun, Jilin Province 130024, ChinaState Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, P. R. ChinaMore by Jiaxue Yu
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- Jingju LiuJingju LiuKey Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education, National & Local United Engineering Laboratory for Power Batteries, Key Laboratory of Nanobiosensing and Nanobioanalysis at Universities of Jilin Province, Analysis and Testing Center, Department of Chemistry, Northeast Normal University, Changchun, Jilin Province 130024, ChinaMore by Jingju Liu
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- Chong-Bo Ma*Chong-Bo Ma*Email: [email protected] (C.B. Ma).Key Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education, National & Local United Engineering Laboratory for Power Batteries, Key Laboratory of Nanobiosensing and Nanobioanalysis at Universities of Jilin Province, Analysis and Testing Center, Department of Chemistry, Northeast Normal University, Changchun, Jilin Province 130024, ChinaMore by Chong-Bo Ma
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- Lijuan QiLijuan QiState Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, P. R. ChinaDepartment of Chemistry, University of Science & Technology of China, Hefei, Anhui 230026, ChinaMore by Lijuan Qi
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- Yan DuYan DuState Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, P. R. ChinaDepartment of Chemistry, University of Science & Technology of China, Hefei, Anhui 230026, ChinaMore by Yan Du
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- Xintong HuXintong HuKey Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun 130021, ChinaMore by Xintong Hu
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- Yanfang Jiang*Yanfang Jiang*Email: [email protected] (Y. Jiang).Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun 130021, ChinaMore by Yanfang Jiang
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- Ming Zhou*Ming Zhou*Email: [email protected] (M. Zhou).Key Laboratory of Polyoxometalate and Reticular Material Chemistry of Ministry of Education, National & Local United Engineering Laboratory for Power Batteries, Key Laboratory of Nanobiosensing and Nanobioanalysis at Universities of Jilin Province, Analysis and Testing Center, Department of Chemistry, Northeast Normal University, Changchun, Jilin Province 130024, ChinaMore by Ming Zhou
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- Erkang WangErkang WangState Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, P. R. ChinaDepartment of Chemistry, University of Science & Technology of China, Hefei, Anhui 230026, ChinaMore by Erkang Wang
Abstract
The present detection method for hepatitis B virus (HBV) drug-resistant mutation has a high misdiagnosis rate and usually needs to meet stringent requirements for technology and equipment, leading to complex and time-consuming manipulation and drawback of high costs. Herein, with the purpose of developing cost-effective, highly efficient, and handy diagnosis for HBV drug-resistant mutants, we propose an electrochemical signal-on strategy through the three-way junction (3WJ) transduction and exonuclease III (Exo III)-assisted catalyzed hairpin assembly (CHA). To achieve single-copy gene detection, loop-mediated nucleic acid isothermal amplification (LAMP), one of the highly promising and compatible techniques to revolutionize point-of-care genetic detection, is first adopted for amplification. The rtN236T mutation, an error encoded by codon 236 of the reverse transcriptase region of HBV DNA, was employed as the model gene target. Under the optimized conditions, it allows end-point transduction from HBV drug-resistant mutants-genomic information to electrochemical signals with ultrahigh sensitivity, specificity, and signal-to-noise ratio, showing the lowest detection concentration down to 2 copies/μL. Such a method provides a possibly new principle for ideal in vitro diagnosis, supporting the construction of a clinic HBV diagnosis platform with high accuracy and generalization. Moreover, it is not restricted by specific nucleic acid sequences but can be applied to the detection of various disease genes, laying the foundation for multiple detection.
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