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AssigneesThe Regents of the University of California, Food and Drug Administration
InventorsNathan Lewis, Wan-Tien Chiang, Montserrat Puig, Yaqin Zhang, Amy Rosenberg
Estimating the term…
A significant interferon (IFN) response is induced following treatment of CHO cells with exogenously-added type I IFN or poly I:C. Treatment of the CHO cells with poly I:C prior to infection limited the cytopathic effect from Vesicular stomatitis virus (VSV), Encephalomyocarditis vims (EMCV), and Reovirus-3 vims (Reo) in a STAT1-dependent manner By knocking out two upstream repressors of STAT1: Gfi1 and Trim 24, the engineered CHO cells exhibited increased resistance to virus contaminations. Thus, omics-guided engineering of mammalian cell culture can be deployed to increase safety in biotherapeutic protein production.
A method of inhibiting viral infection in a biological sample comprising administering to the sample an effective amount of:
A non-naturally occurring mammalian cell culture comprising cells genetically modified for suppressed expression of Gfi1, Trim24 and/or Cb1, and/or activated expression of IRF7, IRF3, STAT1, STAT3, NFATC2, IRF5, STAT4, IRF9, IRF8, NFKB1, TP53, JUN and/or EBF1, as compared to wild-type cells of the same mammalian species.
A method of producing a biopharmaceutical protein from a mammalian cell culture, comprising culturing mammalian cells having non-naturally occurring genetically suppressed expression of Gfi1, Trim24 and/or Cb1, and/or genetically activated expression of IRF7, IRF3, STAT1, STAT3, NFATC2, IRF5, STAT4, IRF9, IRF8, NFKB1, TP53, JUN and/or EBF1, as compared to wild-type cells of the same mammalian species;
A method of treating or preventing viral infection in a mammalian cell comprising administering to the cell an effective amount of:
A method for increasing virus infectivity in a mammalian cell comprising increasing expression of Gfi1, Trim24 or Cb1, and/or decreasing expression of IRF7, IRF3, STAT1, STAT3, NFATC2, IRF5, STAT4, IRF9, IRF8, NFKB1, TP53, JUN and/or EBF1 in the cell.
A non-naturally occurring mammalian cell culture comprising mammalian cells having genetically activated expression of Gfi1, Trim24 or Cb1, and/or genetically suppressed expression of IRF7, IRF3, STAT1, STAT3, NFATC2, IRF5, STAT4, IRF9, IRF8, NFKB1, TP53, JUN and/or EBF1, as compared to wild-type cells of the same mammalian species.
A mammalian cell modified for in vivo suppressed expression or activity of Gfi1, Trim24 and/or Cb1, and/or activated expression or activity of IRF7, IRF3, STAT1, STAT3, NFATC2, IRF5, STAT4, IRF9, IRF8, NFKB1, TP53, JUN and/or EBF1, as compared to wild-type cells of the same mammalian species.
Dependencies are inferred from the claim text.