Specific Binding of a d-RNA G-Quadruplex Structure with an l-RNA Aptamer

G-quadruplex (G4) structures are of general importance in chemistry and biology, such as in biosensing, gene regulation, and cancers. Although a large repertoire of G4-binding tools has been developed, no aptamer has been developed to interact with G4. Moreover, the G4 selectivity of current toolkits is very limited. Herein, we report the first l -RNA aptamer that targets a d -RNA G-quadruplex (rG4). Using TERRA rG4 as an example, our results reveal that this l -RNA aptamer, Ap3-7, folds into a unique secondary structure, exhibits high G4 selectivity and effectively interferes with TERRA-rG4–RHAU53 binding. Our approach and findings open a new door in further developing G4-specific tools for diverse applications.