Journal
BIOTECHNOLOGY PROGRESS
Volume 24, Issue 1, Pages 2-7Publisher
WILEY
DOI: 10.1021/bp070080b
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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 maybe 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.
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