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Generation of a live attenuated influenza A vaccine by proteolysis targeting.
Si, Longlong; Shen, Quan; Li, Jing; Chen, Li; Shen, Jinying; Xiao, Xue; Bai, Haiqing; Feng, Tang; Ye, Adam Yongxin; Li, Le; Zhang, Chunhe; Li, Zhen; Wang, Ping; Oh, Crystal Yuri; Nurani, Atiq; Niu, Siwen; Zhang, Chengxin; Wei, Xiaoqiong; Yuan, Wanqiong; Liao, Hao; Huang, Xiaojie; Wang, Ning; Tian, Wen-Xia; Tian, Hongwei; Li, Li; Liu, Xiaoheng; Plebani, Roberto.
Afiliação
  • Si L; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. ll.si@siat.ac.cn.
  • Shen Q; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • Li J; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • Chen L; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • Shen J; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • Xiao X; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • Bai H; Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, USA.
  • Feng T; Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China.
  • Ye AY; Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Li L; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • Zhang C; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • Li Z; Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, China.
  • Wang P; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • Oh CY; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • Nurani A; Rare Disease Research Unit, Pfizer Inc., Cambridge MA, USA.
  • Niu S; Jnana Therapeutics, Boston, MA, USA.
  • Zhang C; Third Institute of Oceanography, State Oceanic Administration, Xiamen, China.
  • Wei X; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Yuan W; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Liao H; Department of Orthopedics, Peking University Third Hospital, Beijing, China.
  • Huang X; Beijing Key Laboratory of Spinal Disease, Beijing, China.
  • Wang N; Engineering Research Center of Bone and Joint Precision Medicine, Beijing, China.
  • Tian WX; Department of Clinical Laboratory, Shenzhen Third People's Hospital, Southern University of Science and Technology, National Clinical Research Center for Infectious Diseases, Shenzhen, China.
  • Tian H; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • Li L; Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • Liu X; College of Veterinary Medicine, Shanxi Agricultural University, Jinzhong, China.
  • Plebani R; National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Nat Biotechnol ; 40(9): 1370-1377, 2022 09.
Article em En | MEDLINE | ID: mdl-35788567
The usefulness of live attenuated virus vaccines has been limited by suboptimal immunogenicity, safety concerns or cumbersome manufacturing processes and techniques. Here we describe the generation of a live attenuated influenza A virus vaccine using proteolysis-targeting chimeric (PROTAC) technology to degrade viral proteins via the endogenous ubiquitin-proteasome system of host cells. We engineered the genome of influenza A viruses in stable cell lines engineered for virus production to introduce a conditionally removable proteasome-targeting domain, generating fully infective PROTAC viruses that were live attenuated by the host protein degradation machinery upon infection. In mouse and ferret models, PROTAC viruses were highly attenuated and able to elicit robust and broad humoral, mucosal and cellular immunity against homologous and heterologous virus challenges. PROTAC-mediated attenuation of viruses may be broadly applicable for generating live attenuated vaccines.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vacinas contra Influenza / Infecções por Orthomyxoviridae / Influenza Humana Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vacinas contra Influenza / Infecções por Orthomyxoviridae / Influenza Humana Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article