PASylation technology improves recombinant interferon-β1b solubility, stability, and biological activity.
Recombinant interferon-β1b (IFN-β1b) 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-β1b, with PAS sequence at C- or N-terminus of IFN-β1b. 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-β1b. Our results demonstrate that PASylation has a positive impact on stability, solubility, and functional activity of IFN-β1b and potentially might improve pharmacokinetic properties of the molecule as a therapeutic agent.
International Biotechnology Center (IBC) "Generium", Vladimirskaya street 14, Volginsky village, Petushinsky district, Vladimir Region, 601125, Russia. berkovich@ibcgenerium.ru.
Elizaveta A
EA
Zvonova
Generium Pharmaceutical, Testovskaya st. 10, ent. 2, Moscow, 123317, Russia.
Alexander V
AV
Ershov
Generium Pharmaceutical, Testovskaya st. 10, ent. 2, Moscow, 123317, Russia.
Olga A
OA
Ershova
International Biotechnology Center (IBC) "Generium", Vladimirskaya street 14, Volginsky village, Petushinsky district, Vladimir Region, 601125, Russia.
Marina A
MA
Sudomoina
International Biotechnology Center (IBC) "Generium", Vladimirskaya street 14, Volginsky village, Petushinsky district, Vladimir Region, 601125, Russia.
Maksim B
MB
Degterev
International Biotechnology Center (IBC) "Generium", Vladimirskaya street 14, Volginsky village, Petushinsky district, Vladimir Region, 601125, Russia.
Grigoriy N
GN
Poroshin
Cellthera Pharm, Vladimirskaya street 14B, Volginsky village, Petushinsky district, Vladimir Region, 601125, Russia.
Artem V
AV
Eremeev
Cellthera Pharm, Vladimirskaya street 14B, Volginsky village, Petushinsky district, Vladimir Region, 601125, Russia.
Andrey P
AP
Karpov
International Biotechnology Center (IBC) "Generium", Vladimirskaya street 14, Volginsky village, Petushinsky district, Vladimir Region, 601125, Russia.
Alexander Yu
AY
Vishnevsky
Institute of Plant Physiology, Russian Academy of Sciences, ul. Botanicheskaya 35, Moscow, 127276, Russia.
Irina V
IV
Goldenkova-Pavlova
Inbio ventures, Testovskaya st. 10, ent. 2, Moscow, 123317, Russia.
Andrei V
AV
Petrov
Cellthera Pharm, Vladimirskaya street 14B, Volginsky village, Petushinsky district, Vladimir Region, 601125, Russia.
Sergey V
SV
Ruchko
International Biotechnology Center (IBC) "Generium", Vladimirskaya street 14, Volginsky village, Petushinsky district, Vladimir Region, 601125, Russia.
Alexander M
AM
Shuster
D006207:Half-Life; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D000068576:Interferon beta-1b / Q000235:genetics* / Q000378:metabolism* / Q000627:therapeutic use; D009103:Multiple Sclerosis / Q000188:drug therapy; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D012995:Solubility
D007155:Immunologic Factors; D011994:Recombinant Proteins; D000068576:Interferon beta-1b
Biological activity; Expression; Interferon-β1b; PASylation; Solubility; Stability