Conclusions

Living systems rely on the precise control of gene expression to affect appropriate phenotypic responses over different temporal and spatial scales, and therefore maintain proper cellular function. Increased understanding of natural biological systems, in addition to advances in nucleic acid and protein engineering, have inspired researchers to construct synthetic genetic systems and catalyze the emerging field of synthetic biology (1). Recent advances in the field of RNA synthetic biology led to the development of a modular platform from which ligand-responsive ribozyme-based gene-regulatory devices can be assembled (2,3). The ability to construct user-specified ribozyme devices tailored to diverse applications depends on the development and integration of several enabling technologies. Specifically, high throughput technologies that enable the efficient de novo generation of new sensor functions and tailoring of device regulatory properties for specific cellular applications are needed to broaden the utility of these genetic control devices. The ribozyme device platform offers two distinct advantages in advancing our ability to generate new ligand-responsive RNA control devices with tailored regulatory properties. First, the modular composition framework of the device platform supports direct interchange of functional RNA components, including sensors, transmitters, and actuators, to program devices with user-specified regulatory activities. Second, the mechanism of action of the ribozyme component is independent of cell-specific machinery, allowing transport of the resultant ribozyme devices to in vitro or diverse cellular environments. These two advantages allow direct generation and optimization of the individual RNA component activities within the device platform through in vitro and/or in vivo strategies, thereby allowing the development of a scalable framework fro