Synthetic biology: advancing the design of diverse genetic systems

Abstract

A major objective of synthetic biology is to make the process of designing genetically encoded biological systems more systematic, predictable, robust, scalable, and efficient. Examples of genetic systems in the field vary widely in terms of operating hosts, compositional approaches, and network complexity, ranging from simple genetic switches to search-and-destroy systems. While significant advances in DNA synthesis capabilities support the construction of pathway- and genome-scale programs, several design challenges currently restrict the scale of systems that can be reasonably designed and implemented. Thus, while synthetic biology offers much promise in developing systems to address challenges faced in the fields of manufacturing, environment and sustainability, and health and medicine, the realization of this potential is currently limited by the diversity of available parts and effective design frameworks. As researchers make progress in bridging this design gap, advances in the field hint at ever more diverse applications for biological systems.

Figure 1

A single-input, single output (SISO) device. (a) The input/output curve of the SISO device. (b) A transcription-based scheme for implementing SISO. An inducible transcriptional activator is composed of a ligand-binding protein (sensor) fused with an RNA polymerase recruiting domain (regulator). Binding of the input ligand enables the sensor binding to its corresponding promoter region, which turns on gene expression. (c) A posttranscription-based scheme for implementing SISO. An RNA aptamer (sensor) is coupled with a ribozyme (regulator) through an RNA transmitter sequence (adapter). This device is turned on in the presence of input molecule, which binds to the sensor and disrupts the self-cleaving confirmation of the regulator. (d) A posttranslation-based scheme for implementing SISO. A protein destabilizing domain (sensor) is fused directly to the gene-of-interest (actuator) with a peptide linker (adapter). The input ligand can bind to the destabilizing domain; thus prevents the protein from degradation.

Figure 2

Design strategies for engineering genetic devices. Signal types and operating host organisms (indicated in the central circle with green and blue boxes, respectively) are usually determined by the design goal. When designing genetic devices, four major design considerations (the four surrounding sectors) are commonly taken into account.