Abstract: Decades of biochemical studies have advanced DNA beyond its primary role as genetic blueprint.DNAzymes are single-stranded enzymatic DNA molecules that do not exist in nature.They are ideal candidates for gene silencing owing to their scalability by solid-phase synthesis (without batch variations),reprogrammability by directed evolution and local sequence alterations,compatibility with diverse delivery methods,and capability of achieving high catalytic turnover independent of any auxiliary proteins.With these unique features,various artificially evolved DNAzymes have been employed as theranostic tools in designing biosensors and logic gates,RNA/DNA cleavage and ligation,phosphorylation and dephosphorylation,DNA photorepair,and peptide side-chain modifications,to name but a few (Ponce-Salvatierra et al.,2021).This perspective will focus on the functional aspects and therapeutic potentials of RNA-cleaving DNAzymes.