The purpose of this study was to develop a biobetter version of recombinant human interferon-β 1a (rhIFN-β 1a) to improve its biophysical properties, such as aggregation, production and stability, and pharmacokinetic properties without jeopardizing its activity. To achieve this, we introduced additional glycosylation into rhIFN-β 1a via site-directed mutagenesis. Glycoengineering of rhIFN-β 1a resulted in a new molecular entity, termed R27T, which was defined as a rhIFN-β mutein with two N-glycosylation sites at 80th(original site) and at an additional 25thamino acid due to a mutation of Thr for Arg at position 27thof rhIFN-β 1a. Glycoengineering had no effect on rhIFN-β ligand-receptor binding, as no loss of specific activity was observed. R27T showed improved stability and had a reduced propensity for aggregation and an increased half-life. Therefore, hyperglycosylated rhIFN-β could be a biobetter version of rhIFN-β1a with a potential for use as a drug against multiple sclerosis. © 2014 Song et al.
Song, K., Yoon, I. S., Kim, N. A., Kim, D. H., Lee, J., Lee, H. J., … Shin, Y. K. (2014). Glycoengineering of Interferon-β 1a improves its biophysical and pharmacokinetic properties. PLoS ONE, 9(5). https://doi.org/10.1371/journal.pone.0096967