Ligand Engineering via Yeast Surface Display and Adherent Cell Panning

High-throughput ligand discovery and evolution—via genotype-phenotype linkage strategies—empower molecularly targeted therapy, diagnostics, and fundamental science. Maintaining high-quality target antigen in these selections, particularly for membrane targets, is often a technical challenge. Panning yeast-displayed ligand libraries on intact mammalian cells expressing the molecular target has emerged as an effective strategy. Herein we describe the techniques used to select target-binding ligands via this approach including the use of target-negative cells to deplete non-specific binders and avidity reduction to preferentially select high-affinity ligands.