Engineering cell signaling modulators from native protein-protein interactions.

Recent studies on genome sequencing and genetic screens with RNAi and CRISPR technology have revolutionized our understanding of aberrant signaling networks in human diseases. A strategy combining both genetic and protein-based technologies should be at the heart of modern drug-development efforts, particularly in the era of precision medicine. Thus, there is an urgent need for efficient platforms to develop probes that can modulate protein function in cells to validate drug targets and to develop therapeutic leads. Advanced protein engineering has enabled the rapid production of monoclonal antibodies and small protein scaffold affinity reagents for diverse protein targets. Here, we review the most recent progress on engineering natural protein-protein interactions for modulation of cell signaling.