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Catalytic amplification by transition-state molecular switches for direct and sensitive detection of SARS-CoV-2
Despite the importance of nucleic acid testing in managing the COVID-19 pandemic, current detection approaches remain limited due to their high complexity and extensive processing. Here, we describe a molecular nanotechnology that enables direct and sensitive detection of viral RNA targets in native...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968834/ https://www.ncbi.nlm.nih.gov/pubmed/33731349 http://dx.doi.org/10.1126/sciadv.abe5940 |
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author | Sundah, Noah R. Natalia, Auginia Liu, Yu Ho, Nicholas R. Y. Zhao, Haitao Chen, Yuan Miow, Qing Hao Wang, Yu Beh, Darius L. L. Chew, Ka Lip Chan, Douglas Tambyah, Paul A. Ong, Catherine W. M. Shao, Huilin |
author_facet | Sundah, Noah R. Natalia, Auginia Liu, Yu Ho, Nicholas R. Y. Zhao, Haitao Chen, Yuan Miow, Qing Hao Wang, Yu Beh, Darius L. L. Chew, Ka Lip Chan, Douglas Tambyah, Paul A. Ong, Catherine W. M. Shao, Huilin |
author_sort | Sundah, Noah R. |
collection | PubMed |
description | Despite the importance of nucleic acid testing in managing the COVID-19 pandemic, current detection approaches remain limited due to their high complexity and extensive processing. Here, we describe a molecular nanotechnology that enables direct and sensitive detection of viral RNA targets in native clinical samples. The technology, termed catalytic amplification by transition-state molecular switch (CATCH), leverages DNA-enzyme hybrid complexes to form a molecular switch. By ratiometric tuning of its constituents, the multicomponent molecular switch is prepared in a hyperresponsive state—the transition state—that can be readily activated upon the binding of sparse RNA targets to turn on substantial enzymatic activity. CATCH thus achieves superior performance (~8 RNA copies/μl), direct fluorescence detection that bypasses all steps of PCR (<1 hour at room temperature), and versatile implementation (high-throughput 96-well format and portable microfluidic assay). When applied for clinical COVID-19 diagnostics, CATCH demonstrated direct and accurate detection in minimally processed patient swab samples. |
format | Online Article Text |
id | pubmed-7968834 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-79688342021-03-31 Catalytic amplification by transition-state molecular switches for direct and sensitive detection of SARS-CoV-2 Sundah, Noah R. Natalia, Auginia Liu, Yu Ho, Nicholas R. Y. Zhao, Haitao Chen, Yuan Miow, Qing Hao Wang, Yu Beh, Darius L. L. Chew, Ka Lip Chan, Douglas Tambyah, Paul A. Ong, Catherine W. M. Shao, Huilin Sci Adv Research Articles Despite the importance of nucleic acid testing in managing the COVID-19 pandemic, current detection approaches remain limited due to their high complexity and extensive processing. Here, we describe a molecular nanotechnology that enables direct and sensitive detection of viral RNA targets in native clinical samples. The technology, termed catalytic amplification by transition-state molecular switch (CATCH), leverages DNA-enzyme hybrid complexes to form a molecular switch. By ratiometric tuning of its constituents, the multicomponent molecular switch is prepared in a hyperresponsive state—the transition state—that can be readily activated upon the binding of sparse RNA targets to turn on substantial enzymatic activity. CATCH thus achieves superior performance (~8 RNA copies/μl), direct fluorescence detection that bypasses all steps of PCR (<1 hour at room temperature), and versatile implementation (high-throughput 96-well format and portable microfluidic assay). When applied for clinical COVID-19 diagnostics, CATCH demonstrated direct and accurate detection in minimally processed patient swab samples. American Association for the Advancement of Science 2021-03-17 /pmc/articles/PMC7968834/ /pubmed/33731349 http://dx.doi.org/10.1126/sciadv.abe5940 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Sundah, Noah R. Natalia, Auginia Liu, Yu Ho, Nicholas R. Y. Zhao, Haitao Chen, Yuan Miow, Qing Hao Wang, Yu Beh, Darius L. L. Chew, Ka Lip Chan, Douglas Tambyah, Paul A. Ong, Catherine W. M. Shao, Huilin Catalytic amplification by transition-state molecular switches for direct and sensitive detection of SARS-CoV-2 |
title | Catalytic amplification by transition-state molecular switches for direct and sensitive detection of SARS-CoV-2 |
title_full | Catalytic amplification by transition-state molecular switches for direct and sensitive detection of SARS-CoV-2 |
title_fullStr | Catalytic amplification by transition-state molecular switches for direct and sensitive detection of SARS-CoV-2 |
title_full_unstemmed | Catalytic amplification by transition-state molecular switches for direct and sensitive detection of SARS-CoV-2 |
title_short | Catalytic amplification by transition-state molecular switches for direct and sensitive detection of SARS-CoV-2 |
title_sort | catalytic amplification by transition-state molecular switches for direct and sensitive detection of sars-cov-2 |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7968834/ https://www.ncbi.nlm.nih.gov/pubmed/33731349 http://dx.doi.org/10.1126/sciadv.abe5940 |
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