— This paper proposes a synthetic in vitro circuit that aims at regulating the rate of RNA transcription through positive feedback interactions. This design is dual to a previously synthesized transcriptional rate regulator based on self-repression. Two DNA templates are designed to interact through their transcripts, creating cross activating feedback loops that will equate their transcription rates at steady state. A mathematical model is developed for this circuit, consisting of a set of ODEs derived from the mass action laws and Michaelis– Menten kinetics involving all the present chemical species. This circuit is then compared to its regulatory counterpart based on negative feedback. A global sensitivity analysis reveals the fundamental features of the two designs by evaluating their equilibrium response to changes in the most crucial parameters of the system.
Elisa Franco, Richard M. Murray