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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.
  • Wang Y; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Biomedical Synthetic Biology Research Centre, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Dongchuan Road 500, Shanghai, 200241, China.
  • Xu Y; Chongqing Key Laboratory of Precision Optics, Chongqing Institute of East China Normal University, Chongqing, 401120, China.
  • Tan CW; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Biomedical Synthetic Biology Research Centre, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Dongchuan Road 500, Shanghai, 200241, China.
  • Qiao L; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.
  • Chia WN; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Biomedical Synthetic Biology Research Centre, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Dongchuan Road 500, Shanghai, 200241, China.
  • Zhang H; Programme in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore, Singapore.
  • Huang Q; Department of Breast Surgery, Yangpu Hospital, School of Medicine, Tongji University, 450 Tengyue Road, Shanghai, 200090, China.
  • Deng Z; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Biomedical Synthetic Biology Research Centre, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Dongchuan Road 500, Shanghai, 200241, China.
  • Wang Z; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Biomedical Synthetic Biology Research Centre, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Dongchuan Road 500, Shanghai, 200241, China.
  • Wang X; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Biomedical Synthetic Biology Research Centre, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Dongchuan Road 500, Shanghai, 200241, China.
  • Shen X; CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, Hubei, China.
  • Liu C; University of Chinese Academy of Sciences, Beijing, China.
  • Pei R; CAS Key Laboratory of Special Pathogens, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, Hubei, China.
  • Liu Y; University of Chinese Academy of Sciences, Beijing, China.
  • Xue S; University of Chinese Academy of Sciences, Beijing, China.
  • Kong D; State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, Hubei, China.
  • Anderson DE; State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, Hubei, China.
  • Cai F; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Biomedical Synthetic Biology Research Centre, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Dongchuan Road 500, Shanghai, 200241, China.
  • Zhou P; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Biomedical Synthetic Biology Research Centre, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Dongchuan Road 500, Shanghai, 200241, China.
  • Wang LF; Department of Biosystems Science and Engineering, ETH Zurich, CH-4058, Basel, Switzerland.
  • Ye H; Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Biomedical Synthetic Biology Research Centre, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Dongchuan Road 500, Shanghai, 200241, China.
Nat Commun ; 13(1): 7629, 2022 Dec 09.
Article in English | MEDLINE | ID: covidwho-2160211
ABSTRACT
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 ALICESaCas9+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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viruses / Virus Diseases / COVID-19 Type of study: Prognostic study Limits: Animals / Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2022 Document Type: Article Affiliation country: S41467-022-35425-9

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viruses / Virus Diseases / COVID-19 Type of study: Prognostic study Limits: Animals / Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2022 Document Type: Article Affiliation country: S41467-022-35425-9