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Improving Therapeutic Properties of Protein Drugs through Alteration of Intracellular Trafficking Pathways
Author(s) -
Lao Bert J.,
Kamei Daniel T.
Publication year - 2008
Publication title -
biotechnology progress
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.572
H-Index - 129
eISSN - 1520-6033
pISSN - 8756-7938
DOI - 10.1021/bp070080b
Subject(s) - context (archaeology) , function (biology) , intracellular , drug trafficking , drug , microbiology and biotechnology , transport protein , biology , computational biology , pharmacology , paleontology , criminology , sociology
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.