Using a defined medium and a multiple-phage resistant AM-7 strain of Escherichia coli containing a temperature sensitive multicopy plasmid under lambda promoter control, a fermentation process has been developed for an analog human IFN-α that is a “consensus” of the known IFN-α subtypes. The gene for this interferon was completely synthetic and codon choices were optimized for expression in E. coli. Yields up to 7.6 × 1012 U of IFN-α-Con1 per liter of fermentation broth were achieved. The combination of a tightly regulated expression system and a controlled feeding schedule were fundamental to the attainment of the high expression levels and cell densities required to reach this concentration of interferon.
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Fieschko et al. (1986) studied this question.
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