Synthetic ON riboswitch aptamer

The synthetic ON riboswitch aptamer is a specialized RNA-based regulatory element engineered into the genetic sequence of Chimeric Antigen Receptor (CAR) T-cells to provide precise, dose-dependent control over CAR expression [2, 3]. In the Ribo-CAR-T platform, this aptamer acts as a molecular sensor that responds to a specific, orally available small molecule inducer, such as MXU-001 [3, 12]. In the absence of the inducer, the riboswitch adopts a conformation that prevents the translation of the CAR protein, keeping the T-cells in a resting state and reducing the risk of T-cell exhaustion [2, 3]. Upon binding the inducer, the aptamer undergoes a structural shift that activates CAR expression, allowing the T-cells to recognize and eliminate target cells [3, 8]. This technology aims to overcome challenges in CAR-T therapy, such as severe toxicities like cytokine release syndrome, by allowing clinicians to tune the therapeutic activity and switch off the treatment if necessary by withdrawing the drug [2, 3, 6]. The modular nature of the aptamer allows it to be adapted for various ligands and CAR constructs, representing a significant advancement in the safety and efficacy of adoptive cell therapies [6, 8].

Other names

RNA ON-switchRibo-CAR switchLigand-responsive RNA elementSynthetic mammalian riboswitchAptamer-based riboregulator

The synthetic ON riboswitch aptamer functions as a ligand-dependent genetic switch; upon binding a specific small molecule inducer (e.g., MXU-001), the aptamer undergoes a conformational change that enables the translation or stabilization of the Chimeric Antigen Receptor (CAR) mRNA, thereby initiating CAR protein expression and T-cell activation [2, 3, 6].