PASylation technology improves recombinant interferon- beta 1b solubility, stability, and biological activity

Recombinant interferon- beta 1b (IFN- beta 1b) is an effective remedy against multiple sclerosis and other diseases. However, use of small polypeptide (molecular weight is around 18.5 kDa) is limited due to poor solubility, stability, and short half-life in systemic circulation. To solve this problem, we constructed two variants of PASylated IFN- beta 1b, with PAS sequence at C- or N-terminus of IFN- beta 1b. The PAS-modified proteins demonstrated 4-fold increase in hydrodynamic volume of the molecule combined with 2-fold increase of in vitro biological activity, as well as advanced stability and solubility of the protein in solution as opposed to unmodified IFN- beta 1b. Our results demonstrate that PASylation has a positive impact on stability, solubility, and functional activity of IFN- beta 1b and potentially might improve pharmacokinetic properties of the molecule as a therapeutic agent.