Identification of optimal protein binders through the use of large genetically encoded display libraries

•Large genetically encoded binder libraries are displayed on both viruses and cells.•Many binder formats have been selected with high affinity and exquisite specificity for their targets.•Binder improvements beyond the binding site are now addressable.•Developability aspects are now an important consideration in binder design. The use of large genetically encoded binder libraries in co-operation with display technologies has matured over the past 25 years, and is now one of the primary methods used for selection of protein binders. Display technology has proven to be a robust and versatile method for generating binders to almost any antigen of interest. The evolution of this technology beyond antibody phage display has opened up new aspects for the concept of designer biologics. The ability to construct large populations of eukaryotic cells, including mammalian cells, where each cell expresses an individual antibody, peptide or engineered protein has added great value in identifying binders with desired properties. Here we review the evolution of display technology and highlight how it is being used today to generate binders with exquisite specificity, selectivity, affinity and developability characteristics.