— Retroactivity is a parasitic phenomenon that changes the desired input/output response of a system when it is connected to “downstream” systems. Downstream and upstream refer to the direction in which we think the signal is traveling: from upstream to downstream. Transcriptional networks are not immune to this parasitic phenomenon. In this paper, we propose a phosphorylation-based design for a biomolecular system that acts as an insulator between its upstream systems and its downstream ones in a transcriptional network. Performing singular perturbation analysis, we mathematically show that such a design attenuates retroactivity. Stochastic simulations are run to analyze the robustness of the proposed device to biological noise and to highlight design tradeoffs. I. I The concept of retroactivity generalizes the notion of impedance to non-electric systems. It basically describes the amount by which the I/O response of a system is affected by int...