Rapid, highly specific and sensitive detection of human adenovirus using multiple cross displacement amplification coupled with CRISPR-Cas12a-based detection

Human adenoviruses (HAdV), particularly serotypes 3 and 7, are significant pathogens that cause respiratory tract infection. Here, we developed a novel HAdV diagnostic assay, termed HAdV-MCDA-CRISPR, by combining multiple cross displacement amplification (MCDA) with CRISPR/Cas12a-based detection. HA...

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Main Authors: Linglong Wan, Juan Zhou, Lei Yu, Xiaolan Huang, Jin Fu, Fei Xiao, Nan Jia, Yu Zhang, Min Chen, Xu Chen, Zhaomin Feng, Yi Wang, Lihui Meng
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Talanta Open
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666831925000645
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author Linglong Wan
Juan Zhou
Lei Yu
Xiaolan Huang
Jin Fu
Fei Xiao
Nan Jia
Yu Zhang
Min Chen
Xu Chen
Zhaomin Feng
Yi Wang
Lihui Meng
author_facet Linglong Wan
Juan Zhou
Lei Yu
Xiaolan Huang
Jin Fu
Fei Xiao
Nan Jia
Yu Zhang
Min Chen
Xu Chen
Zhaomin Feng
Yi Wang
Lihui Meng
author_sort Linglong Wan
collection DOAJ
description Human adenoviruses (HAdV), particularly serotypes 3 and 7, are significant pathogens that cause respiratory tract infection. Here, we developed a novel HAdV diagnostic assay, termed HAdV-MCDA-CRISPR, by combining multiple cross displacement amplification (MCDA) with CRISPR/Cas12a-based detection. HAdV-MCDA-CRISPR assay uses MCDA to amplify target DNA, followed by detection of predefined sequences using a CRISPR/Cas12a-crRNA complex. Resulting fluorescence from probe cleavage indicates a positive result. A set of 10 MCDA primers and a specific crRNA were designed to ensure high specificity of HAdV-MCDA-CRISPR assay. The entire procedure, including rapid template preparation (∼15 min), MCDA reaction (40 min), and result interpretation (5 min), takes approximately one hour. Targeting the conserved hexon gene, HAdV-MCDA-CRISPR achieves high sensitivity under optimized MCDA reaction conditions (40 min at 66 °C), detecting as little as 1.92 copies/μL of hexon-containing plasmid DNA without cross-reactivity. Validation using 128 clinical samples demonstrated 78/80 positive results for HAdV-positive patients and 48/48 negative results for HAdV-negative patients. Thus, HAdV-MCDA-CRISPR assay offers a promising alternative for rapid and accurate clinical diagnosis of HAdV-3 and HAdV-7 infections.
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spelling doaj-art-a2ae8b87928449daa60fdea6bcc6089f2025-08-20T02:55:20ZengElsevierTalanta Open2666-83192025-08-011110046210.1016/j.talo.2025.100462Rapid, highly specific and sensitive detection of human adenovirus using multiple cross displacement amplification coupled with CRISPR-Cas12a-based detectionLinglong Wan0Juan Zhou1Lei Yu2Xiaolan Huang3Jin Fu4Fei Xiao5Nan Jia6Yu Zhang7Min Chen8Xu Chen9Zhaomin Feng10Yi Wang11Lihui Meng12Experimental Research Center, Capital Center for Children's Health, Capital Medical University, Capital Institute of Pediatrics, Beijing 100020, PR ChinaExperimental Research Center, Capital Center for Children's Health, Capital Medical University, Capital Institute of Pediatrics, Beijing 100020, PR ChinaDepartment of Infection Management, Capital Center for Children's Health, Capital Medical University, Beijing 100020, PR ChinaExperimental Research Center, Capital Center for Children's Health, Capital Medical University, Capital Institute of Pediatrics, Beijing 100020, PR ChinaExperimental Research Center, Capital Center for Children's Health, Capital Medical University, Capital Institute of Pediatrics, Beijing 100020, PR ChinaExperimental Research Center, Capital Center for Children's Health, Capital Medical University, Capital Institute of Pediatrics, Beijing 100020, PR ChinaExperimental Research Center, Capital Center for Children's Health, Capital Medical University, Capital Institute of Pediatrics, Beijing 100020, PR ChinaExperimental Research Center, Capital Center for Children's Health, Capital Medical University, Capital Institute of Pediatrics, Beijing 100020, PR ChinaExperimental Research Center, Capital Center for Children's Health, Capital Medical University, Capital Institute of Pediatrics, Beijing 100020, PR ChinaThe Second Clinical Medical College, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550003, PR China; Department of Scientific Research, The Second Affiliated Hospital, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550003, PR China; Corresponding authors.Beijing Key Laboratory of Surveillance, Early Warning and Pathogen Research on Emerging Infectious Diseases, Beijing Center for Disease Prevention and Control, Beijing 100013, China; Beijing Research Center for Respiratory Infectious Diseases, Beijing 100013, China; Corresponding authors.Experimental Research Center, Capital Center for Children's Health, Capital Medical University, Capital Institute of Pediatrics, Beijing 100020, PR China; Molecular Diagnostic Center, Capital Center for Children's Health, Capital Medical University, Beijing 100020, PR China; Corresponding authors.Department of Infectious Diseases, Capital Center for Children's Health, Capital Medical University, Beijing 100020, PR China; Corresponding authors.Human adenoviruses (HAdV), particularly serotypes 3 and 7, are significant pathogens that cause respiratory tract infection. Here, we developed a novel HAdV diagnostic assay, termed HAdV-MCDA-CRISPR, by combining multiple cross displacement amplification (MCDA) with CRISPR/Cas12a-based detection. HAdV-MCDA-CRISPR assay uses MCDA to amplify target DNA, followed by detection of predefined sequences using a CRISPR/Cas12a-crRNA complex. Resulting fluorescence from probe cleavage indicates a positive result. A set of 10 MCDA primers and a specific crRNA were designed to ensure high specificity of HAdV-MCDA-CRISPR assay. The entire procedure, including rapid template preparation (∼15 min), MCDA reaction (40 min), and result interpretation (5 min), takes approximately one hour. Targeting the conserved hexon gene, HAdV-MCDA-CRISPR achieves high sensitivity under optimized MCDA reaction conditions (40 min at 66 °C), detecting as little as 1.92 copies/μL of hexon-containing plasmid DNA without cross-reactivity. Validation using 128 clinical samples demonstrated 78/80 positive results for HAdV-positive patients and 48/48 negative results for HAdV-negative patients. Thus, HAdV-MCDA-CRISPR assay offers a promising alternative for rapid and accurate clinical diagnosis of HAdV-3 and HAdV-7 infections.http://www.sciencedirect.com/science/article/pii/S2666831925000645Human adenovirusesMultiple cross displacement amplificationCRISPR, Cas12a, crRNA
spellingShingle Linglong Wan
Juan Zhou
Lei Yu
Xiaolan Huang
Jin Fu
Fei Xiao
Nan Jia
Yu Zhang
Min Chen
Xu Chen
Zhaomin Feng
Yi Wang
Lihui Meng
Rapid, highly specific and sensitive detection of human adenovirus using multiple cross displacement amplification coupled with CRISPR-Cas12a-based detection
Talanta Open
Human adenoviruses
Multiple cross displacement amplification
CRISPR, Cas12a, crRNA
title Rapid, highly specific and sensitive detection of human adenovirus using multiple cross displacement amplification coupled with CRISPR-Cas12a-based detection
title_full Rapid, highly specific and sensitive detection of human adenovirus using multiple cross displacement amplification coupled with CRISPR-Cas12a-based detection
title_fullStr Rapid, highly specific and sensitive detection of human adenovirus using multiple cross displacement amplification coupled with CRISPR-Cas12a-based detection
title_full_unstemmed Rapid, highly specific and sensitive detection of human adenovirus using multiple cross displacement amplification coupled with CRISPR-Cas12a-based detection
title_short Rapid, highly specific and sensitive detection of human adenovirus using multiple cross displacement amplification coupled with CRISPR-Cas12a-based detection
title_sort rapid highly specific and sensitive detection of human adenovirus using multiple cross displacement amplification coupled with crispr cas12a based detection
topic Human adenoviruses
Multiple cross displacement amplification
CRISPR, Cas12a, crRNA
url http://www.sciencedirect.com/science/article/pii/S2666831925000645
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