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

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

Automated summary

DNA-encoded peptide/protein libraries are widely used for protein evolutionary modification and peptide/antibody selection. Mammalian cells, with their post-translational modifications and natural conformation, provide a great platform for studying transmembrane proteins or disease-related proteins. However, the construction of large size DNA-encoded libraries in mammalian cells still faces technical challenges. This review summarizes the current progress and applications of DNA-encoded libraries in mammalian cells.