The function of the human interferon-β1a glycan determined in vivo

Lasse Dissing-Olesen*, Morten Thaysen-Andersen, Michael Meldgaard, Peter Højrup, Bente Finsen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)


Recombinant human interferon-β (rhIFN-β) is the leading therapeutic intervention shown to change the cause of relapsing-remitting multiple sclerosis, and both a nonglycosylated and a significantly more active glycosylated variant of rhIFN-β are used in treatment. This study investigates the function of the rhIFN-β1a glycan moiety and its individual carbohydrate residues, using the myxovirus resistance (Mx) mRNA as a biomarker in Mx-congenic mice. We showed that the Mx mRNA level in blood leukocytes peaked 3 h after s.c. administration of rhIFN-β1a. In addition, a clear dose-response relationship was confirmed, and the Mx response was shown to be receptor-mediated. Using specific glycosidases, different glycosylation analogs of rhIFN-β1a were obtained, and their activities were determined. The glycosylated rhIFN-β1a showed significantly higher activity than its deglycosylated counterpart, due to a protein stabilization/solubilization effect of the glycan. It is interesting to note that the terminating sialic acids were essential for these effects. Conclusively, the structure/bioactivity relationship of rhIFN-β1a was determined in vivo, and it provided a novel insight into the role of the rhIFN-β1a glycan and its carbohydrate residues. The possibilities of improving the pharmacological properties of rhIFN-β1a using glycoengineering are discussed.

Original languageEnglish
Pages (from-to)338-347
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number1
Publication statusPublished - Jul 2008
Externally publishedYes


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