Chemical biology of precise RNA targeting and intervention: advances and perspectives

Ribonucleic acid (RNA) is a polymeric molecule that plays dual roles as both a carrier of genetic information and a dynamic regulator in organisms. RNA molecules are attractive targets for functional intervention due to their unique chemical and biological properties, including diverse chemical modifications, high conformational flexibility, and well-defined molecular recognition principles. Recent advancements in chemical biology have significantly expanded the methods for recognizing and manipulating RNA molecules. Here, we provide a summary of chemical and molecular approaches for precise RNA targeting, encompassing oligonucleotide-, small molecule-, CRISPR-, and engineered RNA-binding protein-based tools. We further summarize significant progress in functional RNA intervention, including modulation of epitranscriptomic modifications, site-specific base editing, chemical molecular manipulation, alternative splicing control, RNA degradation, and translational regulation. Finally, we discuss key challenges such as delivery efficiency and target specificity, along with emerging strategies designed to address these limitations. This review provides an overview of the landscape and prospective avenues in RNA targeting and intervention chemical biology, highlighting its significant potential to advance both fundamental research and clinical therapeutics.