Scheme 1. General strategies for synthesis and conditional control of gRNA. (A) General method for RNA modification through site-specific derivatization of PS-2′-OMe. The reaction occurs at PS-2′-OMe without affecting any canonical RNA nucleotide. Aryl = aromatic groups; DMF = N,N-dimethylformamide; r.t. = room temperature. (B) ROS-activated RNA (rosa-RNA) and visible light-activated RNA (vila-RNA) synthesized by the general method using pinacol phenylboronate (BO) and N,N-diethylaminocoumarin (CM) as the aryl groups, respectively. RNA function is interrupted by BO or CM, and can be restored by applying H₂O₂ as ROS or visible light irradiation (hv) at 470 nm. (C) Conditional control of CRISPR-Cas9-mediated gene editing using stimuli-responsive gRNA prepared through the general method. ROS and visible light control is validated with BO-modified and CM-modified crRNA, respectively.