Construction and Applications of Mammalian Cell-Based DNA-Encoded Peptide/Protein Libraries.

DNA-encoded peptide/protein libraries are the starting point for protein evolutionary modification and functional peptide/antibody selection. Different display technologies, protein directed evolution, and deep mutational scanning (DMS) experiments employ DNA-encoded libraries to provide sequence variations for downstream affinity- or function-based selections. Mammalian cells promise the inherent post-translational modification and near-to-natural conformation of exogenously expressed mammalian proteins and thus are the best platform for studying transmembrane proteins or human disease-related proteins. However, due to the current technical bottlenecks of constructing mammalian cell-based large size DNA-encoded libraries, the advantages of mammalian cells as screening platforms have not been fully exploited. In this review, we summarize the current efforts in constructing DNA-encoded libraries in mammalian cells and the existing applications of these libraries in different fields.