Photocatalytic Click Reaction Enhancing RNA Modulation and Reducing CRISPR-Cas9 OFF-Targets

Our study introduces a photocatalytic click chemistry approach, offering a significant advancement over conventional methods in RNA function modulation. This innovative method, utilizing light-activated small molecules, provides a new level of precision and control in RNA regulation, particularly effective in intricate cellular processes. Transitioning this advancement to CRISPR-Cas9 gene editing, we demonstrate its effectiveness in enhancing gene editing specificity and markedly reducing off-target effects. Our approach employs a vinyl ether modification in RNA, activated under visible light with a phenanthrenequinone derivative, creating a CRISPR-OFF switch that precisely regulates CRISPR system activity. This method not only sets a new advancement in genomic interventions but also offers broad applications in gene regulation, paving the way for safer and more reliable gene editing in therapeutic genomics.