Improving therapeutic properties of protein drugs through alteration of intracellular trafficking pathways.
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 drug 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.
Lao
Bert J
BJ
Department of Bioengineering, University of California, Los Angeles, California 90095, USA.
Kamei
Daniel T
DT
D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism / Q000627:therapeutic use; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism / Q000627:therapeutic use; D008954:Models, Biological; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism* / Q000627:therapeutic use*; D015398:Signal Transduction; D014168:Transferrin / Q000378:metabolism / Q000627:therapeutic use
D007141:Immunoglobulin Fc Fragments; D011506:Proteins; D014168:Transferrin; D016179:Granulocyte Colony-Stimulating Factor