Tapping the potential of synthetic riboswitches: reviewing the versatility of the tetracycline aptamer

Synthetic riboswitches are a versatile class of regulatory elements that are becoming increasingly established in synthetic biology applications. They are characterized by their compact size and independence from auxiliary protein factors. While naturally occurring riboswitches were mostly discovered in bacteria, synthetic riboswitches have been designed for all domains of life. Published design strategies far exceed the number of riboswitches found in nature. A core element of any riboswitch is a binding domain, called an aptamer, which is characterized by high specificity and affinity for its ligand. Aptamers can be selected de novo, allowing the design of synthetic riboswitches against a broad spectrum of targets. The tetracycline aptamer has proven to be well suited for riboswitch engineering. Since its selection, it has been used in a variety of applications and is considered to be well established and characterized. Using the tetracycline aptamer as an example, we aim to discuss a large variety of design approaches for synthetic riboswitch engineering and their application. We aim to demonstrate the versatility of riboswitches in general and the high potential of synthetic RNA devices for creating new solutions in both the scientific and medical fields.