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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
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.
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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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