Issue Date: May 15, 2017
Making antibodies minus the cells
Monoclonal antibodies (mAbs)—proteins engineered to bind to particular antigens—can serve as medications for cancer, autoimmune diseases, and other conditions. During mAb development, researchers often tweak the antibody’s underlying DNA sequence and screen for variants that give the highest yields when expressed in cells. Chinese hamster ovary (CHO) cells are typically used to produce these variants for screening, but that process takes a minimum of seven days to express the proteins. Researchers have now taken cells out of the equation to develop a faster, cell-free synthesis platform for making mAbs by modifying the formulation of a commercially available CHO cell extract (ACS Synth. Biol. 2017, DOI: 10.1021/acssynbio.7b00001). Michael C. Jewett of Northwestern University, Varnika Roy of biologics company MedImmune, and colleagues added a glutathione buffer solution and isomerase enzymes to the CHO extract to ensure the correct formation of the disulfide bonds that hold together the antibodies’ four subunits. They then used the system to synthesize mAb-A, a standard antibody used by MedImmune, and confirmed with an assay that it binds its antigen. The cell-free system takes only 24 hours, which could significantly speed up the antibody screening process, the researchers say.
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