Synthetic mammalian ON riboswitch

A synthetic mammalian ON riboswitch is an engineered RNA element designed to provide precise, ligand-dependent control over transgene expression in mammalian cells (Smolke & Silver, 2012, Science). These switches typically consist of a ligand-binding aptamer coupled to an expression platform, such as a ribozyme or an alternative splicing element, which undergoes a conformational change upon ligand binding to activate protein production (Zhong et al., 2016, Nature Chemical Biology). In the ON state, the presence of a specific small molecule inducer stabilizes the mRNA or facilitates translation initiation, thereby increasing the production of the encoded therapeutic protein (MeiraGTx, 2023). This technology is primarily utilized in gene and cell therapies to allow for the tunable delivery of potent biologics, minimizing toxicity associated with constitutive expression (Stifel et al., 2019, RNA Biology). By enabling clinicians to modulate the dosage and timing of a therapy through an oral inducer, synthetic riboswitches enhance the safety and efficacy of advanced medicinal products (Mullard, 2019, Nature Reviews Drug Discovery). Current research focuses on optimizing the dynamic range of these switches and identifying ligands with high bioavailability and low toxicity for clinical use (Chen et al., 2018, Nature Communications).

Other names

RNA switchAptazyme-based switchLigand-responsive riboregulatorSynthetic RNA switchMammalian riboregulator

Ligand binding to the aptamer domain triggers a conformational change in the RNA structure that prevents self-cleavage or releases a translation initiation site, thereby enabling protein synthesis.