An RNA Aptamer Capable of Forming a Hydrogel by Self-Assembly

Hydrogels are supramolecular assemblies with both solute transport properties like liquids and mechanical properties like elastomers. To date, every type of biomolecules except ribonucleic acid (RNA), is capable of forming a hydrogel. Here, we report an RNA that forms a hydrogel by self-assembly. This RNA is originally identified by systematic evolution of ligands by exponential enrichment (SELEX) to enhance the activity of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors as a potential RNA drug for the treatment of cognitive disorders. The RNA hydrogel exhibits an elastic modulus plateau on the order of 10² Pa and shows dynamic RNA chain interactions with relaxation behaviors similar to living wormlike micellar solutions. Small-angle X-ray scattering and cryogenic electron microscopy characterization support the RNA network structures. By sequence mutation and rheological measurements, we reveal two key sequence motifs in the RNA responsible for intermolecular recognition and the formation of a polymer network by self-assembly.