Science · 2013 · 532 citations · 33 references
Life SciencesBioengineeringBiotechnologyGenetic EngineeringSynthetic BiologyTranscriptionGenetic Circuit DesignLogic SynthesisSynthetic Gene CircuitsSynthetic Gene NetworksTranscription In ProkaryotesTranscriptional ControlCell-cell Communication CircuitsDigital Logic CircuitsDna Logic GatesIntegrase ProteinsLogic GatesSequential Logic DesignSynthetic Biology CircuitsTranscription Terminators
Organisms process developmental and environmental signals for survival, and synthetic genetic logic has been engineered to provide simpler, independent control of biological processes. The study aims to develop a three‑terminal transcriptor device that uses bacteriophage serine integrases to control RNA polymerase flow and to enable amplifying logic gates that regulate transcription rates across diverse organisms. The transcriptor operates by integrase‑mediated inversion or deletion of DNA segments encoding transcription terminators or promoters, thereby modulating transcription rates. The authors successfully implemented permanent amplifying AND, NAND, OR, XOR, NOR, and XNOR gates across common control signal ranges, and demonstrated sequential logic that supports autonomous cell‑cell communication of DNA encoding distinct logic‑gate states.
Organisms must process information encoded via developmental and environmental signals to survive and reproduce. Researchers have also engineered synthetic genetic logic to realize simpler, independent control of biological processes. We developed a three-terminal device architecture, termed the transcriptor, that uses bacteriophage serine integrases to control the flow of RNA polymerase along DNA. Integrase-mediated inversion or deletion of DNA encoding transcription terminators or a promoter modulates transcription rates. We realized permanent amplifying AND, NAND, OR, XOR, NOR, and XNOR gates actuated across common control signal ranges and sequential logic supporting autonomous cell-cell communication of DNA encoding distinct logic-gate states. The single-layer digital logic architecture developed here enables engineering of amplifying logic gates to control transcription rates within and across diverse organisms.
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