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

Abstract 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.