Kinetic studies of recombinant human interferon-alpha (rhIFN-α) expression in transient state continuous cultures

Kinetic modeling of rhIFN-α expression was done in continuous cultures using complex media at dilution rates varying from 0.2 to 0.5 h−1. The human IFN-α gene was inserted under the T7 promoter in BL21 (DE3) codon plus (RIL) cells and induced with 1 mM IPTG. Post-induction growth and production profiles were monitored over time. Wash out of the cells was observed only at a dilution rate of 0.5 h−1, which gave a post-induction specific growth rate (μ) of 0.37 h−1. The rate of accumulation of rhIFN-α inside the cells as inclusion bodies was used to calculate the specific product formation rate (qp). qp was found to be strongly correlated with the dilution rates used with the maximum qp being 0.17 g g−1 h−1 at the first hour of induction at a dilution rate of 0.5 h−1.The decline in qp with time could be related to the build up of inclusion bodies inside the cells which reached a maximum value of 50% of the total protein in the fourth hour post-induction.