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Production, formulation and characterization of proteins play a major role in biotechnology industries. We have shown that aqueous arginine solution increases the solubility of proteins in formulation and purification, suppresses aggregation during refolding and storage and improves performance of column chromatography. Acidic arginine solution now finds application for virus inactivation. I will summarize these various effects of arginine on proteins and viruses and describe the current knowledge of the mechanism of the effects of arginine.

A successful development of therapeutic proteins requires a formulation optimal for long-term storage of the proteins. During storage and shipment, proteins are subjected to multiple stresses. Here we show that ciliary neurotrophic factor (CNTF) readily aggregates upon exposure to mechanical stress such as agitation and elevated temperature at 37 degrees C. Sucrose and lysine or arginine protect CNTF from heat stress, while detergents such as Tween20 and organic solvents such as propylene glycol (PG) are effective against agitation. Combination of the amino acids and PG protected the protein from both stresses. The results suggest the importance of combining additives, against multiple stresses, which may have negative as well as positive influence individually against one particular stress.