Development of IFN β-1a versions with reduced immunogenicity and full in vitro biological activity for the treatment of multiple sclerosis

In this study, we applied the DeFT (De-immunization of Functional Therapeutics) approach to producing functional, de-immunized versions of IFNβ-1a. Two de-immunized versions of IFNβ-1a were produced in CHO cells and designated as IFNβ-1a(VAR1) and IFNβ-1a(VAR2). First, the secondary and tertiary protein structures were analyzed by circular dichroism spectroscopy. Then, the variants were also tested for functionality. While IFNβ-1a(VAR2) showed similar in vitro antiviral activity to the original protein, IFNβ-1a(VAR1) exhibited 40% more biological potency. Finally, in vivo assays using HLA-DR transgenic mice revealed that the de-immunized variants showed a markedly reduced immunogenicity when compared to the originator.PMID:37931868 | DOI:10.1016/j.clim.2023.109831
Source: Clinical Immunology - Category: Allergy & Immunology Authors: Source Type: research