Glycoengineering of Interferon-β 1a improves its biophysical and pharmacokinetic properties

Kyoung Song, In Soo Yoon, Nam Ah Kim, Dong Hwan Kim, Jongmin Lee, Hee Jung Lee, Saehyung Lee, Sunghyun Choi, Min Koo Choi, Ha Hyung Kim, Seong Hoon Jeong, Woo Sung Son, Dae Duk Kim, Young Kee Shin

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32 Scopus citations

Abstract

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 25th amino acid due to a mutation of Thr for Arg at position 27th of 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.

Original languageEnglish
Article numbere96967
JournalPLoS ONE
Volume9
Issue number5
DOIs
StatePublished - 23 May 2014

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