Table 5. Recent examples of complex genetic circuits constructed by composing RNA regulators.
| Application area (contribution) | RNA Unit Device | Function | Host | Description | Strategy | Reference |
|---|---|---|---|---|---|---|
| Synthetic Biology (band-pass RNA device) | Small-molecule responsive riboswitches in tandem | Transcriptional and translational control | E. coli | Coupled TTP-OFF riboswitch with another TPP-ON riboswitch in tandem | Two independently in vivo evolved regulators in tandem | 62 |
| Synthetic Biology (RNA device that performs Boolean logic operations) | Small-molecule responsive riboswitches in tandem | Transcriptional and translational control | E. coli | Logic gates AND and NAND1 were engineered by combinations in tandem of a theophylline aptamer fused to thiamine pyrophosphate | Two regulators in tandem independently obtained from a dual genetic screen | 61 |
| Synthetic Biology (RNA adaptor and two devices) | Antisense-inactivating sRNA-like and dual riboregulator (sRNA-like system) | Transcriptional elongation control | E. coli | Use and validation of tnaC2 as a universal converter from translational to transcriptional regulators | Artificial translational initiation regulators coupled to a new adaptor to engineer a transcriptional control device | 1 |
| Synthetic Biology (biocomputers3) | Dual riboregulator (sRNA-like system) | Translational control |
E. coli | Riboregulator engineered previously75 used in two genes tied in a transcriptional cascade | Regulators arranged into a transcriptional cascade | 78 |
| Synthetic Biology (addition to platform/tool box) | Dual riboregulator (sRNA-like system) | Translational initiation control | E. coli | Using same device developed previously75 two complex genetic circuits were constructed: one for multi-sensing and another for metabolic regulation | Rationally designed and in vivo tested diverse RNA regulators variants and arranged in a “switchboard” | 79 |
| Synthetic Biology (Boolean logic operations) | Small-molecule responsive aptazyme | Translational control | E. coli | Translational control by synthetic aptazymes coupled to amber suppression3 generates logic gates | Ligand-binding regulators arranged into complex genetic circuits | 140 |
| Metabolic Engineering (expression of recombinant proteins) | Small-molecule responsive riboswitch | Transcriptional elongation control | B. subtilis | Using the natural glycine tandem riboswitch as a potential gene expression controller | Natural riboswitches fused to actuators tested in vivo | 83 |
1 A logic gate is an imaginary or physical device that performs a Boolean operation. NAND is a logic gate in which the outcome is false only if all the inputs are true. In contrast AND performs a Boolean operation in which both inputs should be true in order for the output to be true as well. 2tnaC: is a regulatory element that contains a Ribosomal Binding Site, short leader peptide code and a rho terminator. 1It is based on the regulatory element from tna operon in E. coli.3Biocomputer: is a DNA, RNA and/or protein-based system capable of performing computational calculations including storing, processing and retrieving data.