Exonuclease-III assisted specific target recognition cooperating with primer exchange reaction for sensitive and label-free microRNA detection

Abstract MicroRNAs (miRNAs) play a crucial regulatory role in biological processes and are closely associated with disease progression. The accurate identification of miRNA biomarkers holds significant potential for early disease diagnosis and therapeutic intervention. In this study, we developed a...

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Main Authors: Xiaoqin Fu, Xiaoyan Fu, Didi Wu, Yunyao Lu
Format: Article
Language:English
Published: SpringerOpen 2025-05-01
Series:Journal of Analytical Science and Technology
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Online Access:https://doi.org/10.1186/s40543-025-00494-0
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author Xiaoqin Fu
Xiaoyan Fu
Didi Wu
Yunyao Lu
author_facet Xiaoqin Fu
Xiaoyan Fu
Didi Wu
Yunyao Lu
author_sort Xiaoqin Fu
collection DOAJ
description Abstract MicroRNAs (miRNAs) play a crucial regulatory role in biological processes and are closely associated with disease progression. The accurate identification of miRNA biomarkers holds significant potential for early disease diagnosis and therapeutic intervention. In this study, we developed a highly sensitive and label-free method for detecting miRNA-21, a well-established cancer biomarker, by combining exonuclease III (Exo-III)- assisted target recycling with primer exchange reaction (PER). Initially, the target miRNA hybridizes with the probe complex (PC), forming a blunt-end structure that is recognized and cleaved by Exo-III. Through Exo-III-mediated recycling, the released PER template binds to primer-conjugated magnetic beads (primer@MBs), initiating a polymerase-assisted PER amplification process. This reaction generates a substantial number of G-quadruplex sequences, which subsequently bind to thioflavin T (ThT), leading to a dramatic enhancement in fluorescence signal for miRNA-21 detection. The proposed method achieves an exceptionally low detection limit of 2.03 fM while maintaining high specificity for miRNA-21. Furthermore, the integration of magnetic bead (MB)-based enrichment and separation significantly reduces interference from nonspecific molecules, thereby enhancing the assay’s stability and reproducibility. Owing to its label-free design, high sensitivity, and selectivity, this approach offers a robust and versatile platform for the early detection of various disease-related biomarkers.
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institution Kabale University
issn 2093-3371
language English
publishDate 2025-05-01
publisher SpringerOpen
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series Journal of Analytical Science and Technology
spelling doaj-art-e04ff5935af94a41b26a2734d8694ef42025-08-20T03:48:18ZengSpringerOpenJournal of Analytical Science and Technology2093-33712025-05-011611810.1186/s40543-025-00494-0Exonuclease-III assisted specific target recognition cooperating with primer exchange reaction for sensitive and label-free microRNA detectionXiaoqin Fu0Xiaoyan Fu1Didi Wu2Yunyao Lu3Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer HospitalChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer HospitalChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer HospitalChongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer HospitalAbstract MicroRNAs (miRNAs) play a crucial regulatory role in biological processes and are closely associated with disease progression. The accurate identification of miRNA biomarkers holds significant potential for early disease diagnosis and therapeutic intervention. In this study, we developed a highly sensitive and label-free method for detecting miRNA-21, a well-established cancer biomarker, by combining exonuclease III (Exo-III)- assisted target recycling with primer exchange reaction (PER). Initially, the target miRNA hybridizes with the probe complex (PC), forming a blunt-end structure that is recognized and cleaved by Exo-III. Through Exo-III-mediated recycling, the released PER template binds to primer-conjugated magnetic beads (primer@MBs), initiating a polymerase-assisted PER amplification process. This reaction generates a substantial number of G-quadruplex sequences, which subsequently bind to thioflavin T (ThT), leading to a dramatic enhancement in fluorescence signal for miRNA-21 detection. The proposed method achieves an exceptionally low detection limit of 2.03 fM while maintaining high specificity for miRNA-21. Furthermore, the integration of magnetic bead (MB)-based enrichment and separation significantly reduces interference from nonspecific molecules, thereby enhancing the assay’s stability and reproducibility. Owing to its label-free design, high sensitivity, and selectivity, this approach offers a robust and versatile platform for the early detection of various disease-related biomarkers.https://doi.org/10.1186/s40543-025-00494-0microRNAPrimer exchange reactionExonuclease-IIIThioflavin TG-quadruplex
spellingShingle Xiaoqin Fu
Xiaoyan Fu
Didi Wu
Yunyao Lu
Exonuclease-III assisted specific target recognition cooperating with primer exchange reaction for sensitive and label-free microRNA detection
Journal of Analytical Science and Technology
microRNA
Primer exchange reaction
Exonuclease-III
Thioflavin T
G-quadruplex
title Exonuclease-III assisted specific target recognition cooperating with primer exchange reaction for sensitive and label-free microRNA detection
title_full Exonuclease-III assisted specific target recognition cooperating with primer exchange reaction for sensitive and label-free microRNA detection
title_fullStr Exonuclease-III assisted specific target recognition cooperating with primer exchange reaction for sensitive and label-free microRNA detection
title_full_unstemmed Exonuclease-III assisted specific target recognition cooperating with primer exchange reaction for sensitive and label-free microRNA detection
title_short Exonuclease-III assisted specific target recognition cooperating with primer exchange reaction for sensitive and label-free microRNA detection
title_sort exonuclease iii assisted specific target recognition cooperating with primer exchange reaction for sensitive and label free microrna detection
topic microRNA
Primer exchange reaction
Exonuclease-III
Thioflavin T
G-quadruplex
url https://doi.org/10.1186/s40543-025-00494-0
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AT xiaoyanfu exonucleaseiiiassistedspecifictargetrecognitioncooperatingwithprimerexchangereactionforsensitiveandlabelfreemicrornadetection
AT didiwu exonucleaseiiiassistedspecifictargetrecognitioncooperatingwithprimerexchangereactionforsensitiveandlabelfreemicrornadetection
AT yunyaolu exonucleaseiiiassistedspecifictargetrecognitioncooperatingwithprimerexchangereactionforsensitiveandlabelfreemicrornadetection