A review of methods to increase the stability of recombinant pharmaceutical proteins during the production and storage process

Abstract

The production of biotechnological drug proteins plays an important role against disease. The process of producing drug recombinant proteins is not a direct path, because it requires a lot of work and on the other hand, one of the important and significant aspects in the production of proteins is the discussion of their stability and solubility during the expression and purification process. Proteins are stable only in a limited range of temperature and acidity conditions and are highly susceptible to physical and chemical degradation. Today, various solutions have been proposed to increase the solubility and stability of proteins, including guided changes in the protein molecule, and optimization of the instructions for expression, purification and solubility of proteins, which is often the first approach that is not possible. This review article provides solutions to increase the stability of proteins at different levels, including the study of the effect of expression construct design, protein tags and sequences on stability, optimal host cell selection and improved expression conditions. The effect of optimizing buffers used in pharmaceutical formulations such as selecting appropriate amino acids and osmolytes to increase protein stability and how sugars and polyols affect the stability of recombinant pharmaceutical proteins is also investigated.