Improving Therapeutic Properties of Protein Drugs through Alteration of Intracellular Trafficking Pathways

摘要

Although intracellular trafficking processes can play a central role in the physiological function of a protein,these same processes can also limit the benefit of the protein when it is taken out of its physiological context and used as a protein drug.Therefore,the properties of certain protein drugs may be improved by manipulating their trafficking pathways to suit their therapeutic function.A detailed consideration of the factors that govern how protein traffic is routed among different cellular destinations can be used to ascertain molecular design criteria for engineering a protein drug so as to alter its trafficking pathway in a beneficial manner.In this review,we summarize studies that have applied this approach to achieve the following three improvements in protein drag function:(1)half-life extension of the Fc fragment of IgG,(2)half-life extension of granulocyte colony-stimulating factor,and(3)increase in cellular association of transferrin.