Expression systems for therapeutic glycoprotein production.
There are slightly over 165 recombinant pharmaceuticals currently approved for human use. Another 500 protein candidates are in preclinical and clinical development, about 70% of these being glycosylated proteins. The need for expression systems allowing the efficient manufacturing of high quality glycoproteins is thus becoming imperative. Recent developments with CHO cells, the predominant mammalian expression system, have focused on either increasing cell specific productivity or prolonging the life span of cells in culture that translates to high integrated viable cell densities. These two factors have allowed volumetric productivities in excess of 5 g/L under conditions of controlled nutrient feeding. In addition to glycoengineering strategies, which are offering considerable advantage in producing proteins with enhanced therapeutic properties, several alternative expression systems are being developed for their manufacture, each with their advantages and limitations.
Durocher
Yves
Y
Animal Cell Technology Group, Biotechnology Research Institute, National Research Council Canada, 6100 Royalmount Avenue, Montreal (QC) H4P2R2, Canada. yves.durocher@nrc-cnrc.gc.ca
Butler
Michael
M
D000818:Animals; D001702:Biopharmaceutics / Q000379:methods*; D016466:CHO Cells; D049109:Cell Proliferation; D002470:Cell Survival; D002626:Chemistry, Pharmaceutical / Q000379:methods; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D006023:Glycoproteins / Q000737:chemistry*; D006801:Humans; D007313:Insecta; D010944:Plants; D015202:Protein Engineering / Q000379:methods; D011994:Recombinant Proteins / Q000737:chemistry*
D006023:Glycoproteins; D011994:Recombinant Proteins