RNA chemistry and therapeutics

RNA-based therapeutics have made substantial clinical advances, primarily due to the unique chemical and biological profiles of RNA molecules. As evidenced by the approval of various RNA drugs, some initial challenges related to RNA-based therapeutics, including issues associated with large-scale production, effective delivery and immunogenicity properties, are now being addressed. Extensive efforts have focused on chemically modifying RNA molecules to enhance their stability, increase protein production, extend circulation time and improve target specificity. Three RNA categories — small RNA, translatable RNA and CRISPR guide RNA — are now being extensively developed for therapeutic applications. This Review summarizes the synthetic methods applied to these three RNA categories, describes key chemical modification strategies being used to enhance their properties and highlights current therapeutic applications and future opportunities.