The complex phenotypes of eukaryotic cells are controlled bydecision-making circuits and signaling pathways.A key obstacleto implementing artificial connections in signaling networkshas been the lack of synthetic devices for efficient sensing,processing and controlof biological signals.By extendingsgRNAs to include modified riboswitches that recognize specificsignals,we can create CRISPR–Cas9-based signal conductorsthat regulate transcription of endogenous genes in responseto external or internal signals of interest.These devices can beused to construct all the basic types of Boolean logic gates thatperform logical signal operations in mammalian cells withoutneeding the layering of multiple genetic circuits.They canalso be used to rewire cellular signaling events by constructingsynthetic links that couple different signaling pathways.Moreover,this approach can be applied to redirect oncogenicsignal transduction by controlling simultaneous bidirectional(ON–OFF)gene transcriptions,thus enabling reprogrammingof the fate of cancer cells.