Beyond affinity: antibody discovery, optimization, and developability screening from mammalian display libraries

Clinical drug candidates must have not only appropriate affinity and target specificity, but also optimal biophysical properties. Using nuclease-directed integration, we constructed large mammalian display libraries where each cell contains a single antibody gene inserted at a single locus. IgG-formatted antibodies are displayed on the surface, permitting selection from the library of clones by FACS, which allows the selection for desirable binding properties in the final format. This system is uniquely sensitive to critical biophysical characteristics, such as aggregation propensity and poly-specificity, thereby enabling the detection and avoidance of problematic antibodies during the initial discovery phase.

 

 

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