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Engineering antiviral immune-like systems for autonomous virus detection and inhibition in mice
The ongoing COVID-19 pandemic has demonstrated that viral diseases represent an enormous public health and economic threat to mankind and that individuals with compromised immune systems are at greater risk of complications and death from viral diseases. The development of broad-spectrum antivirals...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9734111/ https://www.ncbi.nlm.nih.gov/pubmed/36494373 http://dx.doi.org/10.1038/s41467-022-35425-9 |
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author | Wang, Yidan Xu, Ying Tan, Chee Wah Qiao, Longliang Chia, Wan Ni Zhang, Hongyi Huang, Qin Deng, Zhenqiang Wang, Ziwei Wang, Xi Shen, Xurui Liu, Canyu Pei, Rongjuan Liu, Yuanxiao Xue, Shuai Kong, Deqiang Anderson, Danielle E. Cai, Fengfeng Zhou, Peng Wang, Lin-Fa Ye, Haifeng |
author_facet | Wang, Yidan Xu, Ying Tan, Chee Wah Qiao, Longliang Chia, Wan Ni Zhang, Hongyi Huang, Qin Deng, Zhenqiang Wang, Ziwei Wang, Xi Shen, Xurui Liu, Canyu Pei, Rongjuan Liu, Yuanxiao Xue, Shuai Kong, Deqiang Anderson, Danielle E. Cai, Fengfeng Zhou, Peng Wang, Lin-Fa Ye, Haifeng |
author_sort | Wang, Yidan |
collection | PubMed |
description | The ongoing COVID-19 pandemic has demonstrated that viral diseases represent an enormous public health and economic threat to mankind and that individuals with compromised immune systems are at greater risk of complications and death from viral diseases. The development of broad-spectrum antivirals is an important part of pandemic preparedness. Here, we have engineer a series of designer cells which we term autonomous, intelligent, virus-inducible immune-like (ALICE) cells as sense-and-destroy antiviral system. After developing a destabilized STING-based sensor to detect viruses from seven different genera, we have used a synthetic signal transduction system to link viral detection to the expression of multiple antiviral effector molecules, including antiviral cytokines, a CRISPR-Cas9 module for viral degradation and the secretion of a neutralizing antibody. We perform a proof-of-concept study using multiple iterations of our ALICE system in vitro, followed by in vivo functionality testing in mice. We show that dual output ALICE(SaCas9+Ab) system delivered by an AAV-vector inhibited viral infection in herpetic simplex keratitis (HSK) mouse model. Our work demonstrates that viral detection and antiviral countermeasures can be paired for intelligent sense-and-destroy applications as a flexible and innovative method against virus infection. |
format | Online Article Text |
id | pubmed-9734111 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-97341112022-12-11 Engineering antiviral immune-like systems for autonomous virus detection and inhibition in mice Wang, Yidan Xu, Ying Tan, Chee Wah Qiao, Longliang Chia, Wan Ni Zhang, Hongyi Huang, Qin Deng, Zhenqiang Wang, Ziwei Wang, Xi Shen, Xurui Liu, Canyu Pei, Rongjuan Liu, Yuanxiao Xue, Shuai Kong, Deqiang Anderson, Danielle E. Cai, Fengfeng Zhou, Peng Wang, Lin-Fa Ye, Haifeng Nat Commun Article The ongoing COVID-19 pandemic has demonstrated that viral diseases represent an enormous public health and economic threat to mankind and that individuals with compromised immune systems are at greater risk of complications and death from viral diseases. The development of broad-spectrum antivirals is an important part of pandemic preparedness. Here, we have engineer a series of designer cells which we term autonomous, intelligent, virus-inducible immune-like (ALICE) cells as sense-and-destroy antiviral system. After developing a destabilized STING-based sensor to detect viruses from seven different genera, we have used a synthetic signal transduction system to link viral detection to the expression of multiple antiviral effector molecules, including antiviral cytokines, a CRISPR-Cas9 module for viral degradation and the secretion of a neutralizing antibody. We perform a proof-of-concept study using multiple iterations of our ALICE system in vitro, followed by in vivo functionality testing in mice. We show that dual output ALICE(SaCas9+Ab) system delivered by an AAV-vector inhibited viral infection in herpetic simplex keratitis (HSK) mouse model. Our work demonstrates that viral detection and antiviral countermeasures can be paired for intelligent sense-and-destroy applications as a flexible and innovative method against virus infection. Nature Publishing Group UK 2022-12-09 /pmc/articles/PMC9734111/ /pubmed/36494373 http://dx.doi.org/10.1038/s41467-022-35425-9 Text en © The Author(s) 2022, corrected publication 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Wang, Yidan Xu, Ying Tan, Chee Wah Qiao, Longliang Chia, Wan Ni Zhang, Hongyi Huang, Qin Deng, Zhenqiang Wang, Ziwei Wang, Xi Shen, Xurui Liu, Canyu Pei, Rongjuan Liu, Yuanxiao Xue, Shuai Kong, Deqiang Anderson, Danielle E. Cai, Fengfeng Zhou, Peng Wang, Lin-Fa Ye, Haifeng Engineering antiviral immune-like systems for autonomous virus detection and inhibition in mice |
title | Engineering antiviral immune-like systems for autonomous virus detection and inhibition in mice |
title_full | Engineering antiviral immune-like systems for autonomous virus detection and inhibition in mice |
title_fullStr | Engineering antiviral immune-like systems for autonomous virus detection and inhibition in mice |
title_full_unstemmed | Engineering antiviral immune-like systems for autonomous virus detection and inhibition in mice |
title_short | Engineering antiviral immune-like systems for autonomous virus detection and inhibition in mice |
title_sort | engineering antiviral immune-like systems for autonomous virus detection and inhibition in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9734111/ https://www.ncbi.nlm.nih.gov/pubmed/36494373 http://dx.doi.org/10.1038/s41467-022-35425-9 |
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