Engineering protein stability
Two American teams have proposed distinct strategies to improve the stability of recombinant proteins. The techniques could be used to increase the manufacturing yield, shelf life and potentially the duration of efficacy of biologics, including antibodies and therapeutic cytokines.
Efforts to improve a protein's stability typically require the production of hundreds of variants and characterization of their biophysical properties in vitro in order to choose the best variant. The two new techniques are expected to be applicable to a range of proteins and could stabilize antibodies and therapeutic cytokines more quickly and efficiently than current methods (see "Two approaches for improving protein stability").
A team at The Scripps Research Institute uncovered an amino acid sequence that, when placed near glycosylation sites, helps stiffen the protein's backbone.1 This stabilizing amino acid sequence proved transplantable into nonglycosylated proteins, allowing them to become glycosylated and stabilized.
Pfizer Inc.already has obtained a license to the approach.
Meanwhile, a group at the Massachusetts Institute of Technology devised an enzymaticscheme to join thetwo ends of small cytokines like interferon-a2 (IFNA2; IFN-a2), G-CSF (CSF3) and erythropoietin (EPO) and tag them with the stabilizing molecule polyethylene glycol (PEG). The resulting pegylated circular proteinsretain all of their biological activity but