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Technology

Devices based on RBPs can be easily wired together to create synthetic circuits of various complexities or to interconnect cellular and synthetic signaling pathways. The design to control protein expression includes two translational repressors, L7Ae, which blocks ribosome scanning if placed in the 3' ultrasound region (3'UTR), and a fusion protein MS2-CNOT7. MS2 is another RNA binding coat protein from bacteriophage, MS2, and CNOT7 is a human deadenylase that can efficiently repress translation of mRNA. This platform provides a plug-and play post-transcriptional regulation framework through an engineered set of diverse regulatory circuits including a multi-input cell type classifier, a cascade, and a two state switch. For instance, the Inventors have designed a circuit that recognizes a microRNA profile that is specific for Hela cells and it only triggers a response if the profile is matched, which if the response includes a pro-apoptotic gene, can selectively induce apoptosis in Hela cells. Tunable expression of RNA agents can also be achieved using aptamers or a cascade and a switch between two different therapeutic agents.