Exploring Protein Aggregation in Biological Products: From Mechanistic Understanding to Practical Solutions.

Proteins are vital for the regulation of several cellular functions, including the synthesis of structural components. The change in environmental conditions will impact conformational stability and result in aggregation. Protein aggregation involves different states of proteins, like nonnative, unfolded, and native states, which make them complex processes. The proper understanding of protein aggregation pathways involving the role of thermodynamically unfavoured lag phase, soluble protofibrils triggered polymerization through an exponential phase, and depleted free monomers owing to the saturation phase resulted in the leveling off of the polymerization process. The aggregated therapeutic proteins can induce deleterious immune responses in patients, and control of the aggregation is essential for better therapeutic protein stability and targeting with the help of stable protein structures and function. Protein-protein interactions (PPIs) are important for protein stability, aggregation rate, and solubility, while advanced computational and biophysical methods have been developed to characterize therapeutic protein aggregation better. Hence, an effective strategy for controlling, monitoring, and reproducing protein aggregation propensities of the polypeptide chains is required. An in-depth understanding of protein aggregation mechanisms, characterization, and combat strategies will counter the issues of protein aggregation. It will also reduce the cost of the product, time constraints, stable & effective product availability, and potential immunogenicity.