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PLoS One. 2014 May 23;9(5):e96967. doi: 10.1371/journal.pone.0096967. eCollection 2014.

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

Author information

1
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea; Research Institute of Reference Biolabs. Inc., Seoul, Republic of Korea.
2
College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam, Republic of Korea.
3
College of Pharmacy, Dongguk University-Seoul, Gyeonggi-do, Republic of Korea.
4
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
5
PanGen Biotech Inc., Gyeonggi-do, Republic of Korea.
6
Research Institute of Reference Biolabs. Inc., Seoul, Republic of Korea.
7
College of Pharmacy, DanKook University, Chungnam, Republic of Korea.
8
Biotherapeutics and Glycomics Laboratory, College of Pharmacy, Chung-Ang University, Seoul, Republic of Korea.
9
College of Pharmacy, CHA University, Gyeonggi-do, Republic of Korea.
10
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea; Institutes of Entrepreneurial BioConvergence, Seoul National University, Seoul, Republic of Korea.

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-β 1a with a potential for use as a drug against multiple sclerosis.

PMID:
24858932
PMCID:
PMC4032242
DOI:
10.1371/journal.pone.0096967
[Indexed for MEDLINE]
Free PMC Article

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