Enhanced interferon‐β production by CHO cells through elevated osmolality and reduced culture temperature

For efficient production of native interferon‐β (IFN‐β) in recombinant CHO cell culture, the IFN‐β molecular aggregation that occurs during culture needs to be minimized. To do so, we investigated the effect of hyperosmolality and hypothermia on IFN‐β production and molecular aggregation in rCHO cell culture. Both hyperosmolality (470 mOsm/kg) and hypothermia (32°C) increased specific native INF‐β productivity q IFN‐β . Furthermore, they decreased the IFN‐β molecular aggregation, although severe IFN‐β molecular aggregation could not be avoided in the later phase of culture. To overcome growth suppression at hyperosmolality and hypothermia, cells were cultivated in a biphasic mode. Cells were first cultivated at 310 mOsm/kg and 37°C for 2 days to rapidly obtain a reasonably high cell concentration. The temperature and osmolality were then shifted to 32°C and 470 mOsm/kg, respectively, to achieve high q IFN‐β and reduced IFN‐β molecular aggregation. Due to the enhanced q IFN‐β and delayed molecular aggregation, the highest native IFN‐β concentration achieved on day 6 was 18.03 ± 0.61 mg/L, which was 5.30–fold higher than that in a control batch culture (310 mOsm/kg and 37°C). Taken together, a combination of hyperosmolality and hypothermia in a biphasic culture is a useful strategy for improved native IFN‐β production from rCHO cells. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009