Designing Synthetic Regulatory RNAs: New Tools for Temporal and Spatial Control in Biological Systems

Abstract

Advances in synthetic biology are transforming our ability to design and build synthetic biological systems. While progress has been made in the design of complex genetic circuits, capabilities for constructing large genetic systems currently surpass our ability to design such systems. This growing ‘design gap’ has highlighted the need to develop methods that support the generation of new functional biological components and scalable design strategies for complex genetic circuits that will lay the foundation for integrated biological devices and systems.As examples of functional RNA molecules playing key roles in the behavior of natural biological systems have grown over the past decade, there has been growing interest in the design and implementation of synthetic counterparts. Researchers are taking advantage of the relative ease with which RNA molecules can be modeled and designed to engineer functional RNA molecules that act as diverse components including sensors, regulators, controllers (ligand-responsive RNA regulators), and scaffolds. These synthetic regulatory RNAs are providing new tools for temporal and spatial control in biological systems. I will describe recent advances in the design of RNA controllers and in addressing challenges in their implementation as user-programmed cellular control systems. In particular, I will discuss how the application of synthetic RNA controllers in biological pathways is leading to the elucidation of integrated systems design strategies and new capabilities for programming genetic systems.