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New genetically encoded biosensors utilizing the modified firefly luciferase promise a great improvement in the signal-to-noise ratio and the dynamic range of response in living cells. These biosensors are particularly suitable for high-throughput screening assays that use large-well-capacity formats because of their excellent response characteristics. The biosensor design strategies are highly generalizable and will be extremely valuable for expanding the repertoire of screenable targets in living cell systems.

New Approaches to In-Cell Detection of Protein Activity: Genetically Encoded Chemiluminescence Probes Pave the Way to Robust HTS Assays