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Combating viral contaminants in CHO cells by engineering innate immunity.
Chiang, Austin W T; Li, Shangzhong; Kellman, Benjamin P; Chattopadhyay, Gouri; Zhang, Yaqin; Kuo, Chih-Chung; Gutierrez, Jahir M; Ghazi, Faezeh; Schmeisser, Hana; Ménard, Patrice; Bjørn, Sara Petersen; Voldborg, Bjørn G; Rosenberg, Amy S; Puig, Montserrat; Lewis, Nathan E.
Afiliação
  • Chiang AWT; Department of Pediatrics, University of California, San Diego, La Jolla, CA, 92093, USA.
  • Li S; The Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, La Jolla, CA, 92093, USA.
  • Kellman BP; The Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, La Jolla, CA, 92093, USA.
  • Chattopadhyay G; Department of Bioengineering, University of California, San Diego, La Jolla, CA, 92093, USA.
  • Zhang Y; Department of Pediatrics, University of California, San Diego, La Jolla, CA, 92093, USA.
  • Kuo CC; The Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, La Jolla, CA, 92093, USA.
  • Gutierrez JM; Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA, 92093, USA.
  • Ghazi F; Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.
  • Schmeisser H; Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, 20993, USA.
  • Ménard P; Department of Pediatrics, University of California, San Diego, La Jolla, CA, 92093, USA.
  • Bjørn SP; The Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, La Jolla, CA, 92093, USA.
  • Voldborg BG; Department of Bioengineering, University of California, San Diego, La Jolla, CA, 92093, USA.
  • Rosenberg AS; Department of Pediatrics, University of California, San Diego, La Jolla, CA, 92093, USA.
  • Puig M; The Novo Nordisk Foundation Center for Biosustainability at the University of California, San Diego, La Jolla, CA, 92093, USA.
  • Lewis NE; Department of Bioengineering, University of California, San Diego, La Jolla, CA, 92093, USA.
Sci Rep ; 9(1): 8827, 2019 06 20.
Article em En | MEDLINE | ID: mdl-31222165
ABSTRACT
Viral contamination in biopharmaceutical manufacturing can lead to shortages in the supply of critical therapeutics. To facilitate the protection of bioprocesses, we explored the basis for the susceptibility of CHO cells to RNA virus infection. Upon infection with certain ssRNA and dsRNA viruses, CHO cells fail to generate a significant interferon (IFN) response. Nonetheless, the downstream machinery for generating IFN responses and its antiviral activity is intact in these cells treatment of cells with exogenously-added type I IFN or poly IC prior to infection limited the cytopathic effect from Vesicular stomatitis virus (VSV), Encephalomyocarditis virus (EMCV), and Reovirus-3 virus (Reo-3) in a STAT1-dependent manner. To harness the intrinsic antiviral mechanism, we used RNA-Seq to identify two upstream repressors of STAT1 Gfi1 and Trim24. By knocking out these genes, the engineered CHO cells exhibited activation of cellular immune responses and increased resistance to the RNA viruses tested. Thus, omics-guided engineering of mammalian cell culture can be deployed to increase safety in biotherapeutic protein production among many other biomedical applications.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Microbiologia Industrial / Engenharia Genética / Células CHO / Interações Hospedeiro-Patógeno / Imunidade Inata Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Microbiologia Industrial / Engenharia Genética / Células CHO / Interações Hospedeiro-Patógeno / Imunidade Inata Idioma: En Ano de publicação: 2019 Tipo de documento: Article