Synthetic ON riboswitch aptamer (MXU-001 responsive) (MXU-001-aptamer)

The Synthetic ON riboswitch aptamer is an engineered RNA regulatory element utilized in the Ribo-CAR-T platform to provide precise, small-molecule-mediated control over immunotherapy. This aptamer is specifically designed to recognize and bind MXU-001, a proprietary small molecule inducer developed by MeiraGTx. When integrated into the mRNA of a Chimeric Antigen Receptor (CAR), the aptamer functions as a switch that remains in the 'off' state until the inducer is present. Binding of MXU-001 triggers a structural rearrangement in the riboswitch, allowing for the translation or proper splicing of the CAR mRNA and subsequent expression of the receptor on the T-cell surface. This technology aims to enhance the safety of CAR-T therapies by allowing clinicians to modulate the intensity of the immune response or deactivate it entirely if toxicities like Cytokine Release Syndrome (CRS) occur. It represents a significant advancement in synthetic biology applied to precision medicine and cell therapy (MeiraGTx, 2023; ASGCT, 2024).

Other names

MeiraGTx riboswitch aptamerMXU-001 responsive RNA switchRibo-CAR-T control elementSynthetic mammalian riboswitch

The aptamer acts as a molecular sensor within a synthetic riboswitch construct. In the absence of the small molecule inducer MXU-001, the riboswitch prevents the expression of the Chimeric Antigen Receptor (CAR) by inducing alternative splicing or inhibiting translation. Upon administration and binding of MXU-001 to the aptamer, the RNA undergoes a conformational change that enables the production of functional CAR protein, thereby activating the T-cell's therapeutic activity.