IRES-Mediated Translation: Expanding the Toolkits of RNA Therapy

RNA therapy appears to be a promising strategy to treat various diseases. In recent years, mRNA vaccines have shown notable efficacy in preclinical studies for cancer vaccines, autoimmune disease, and pandemic intervention. Internal ribosome entry sites (IRESs) are structured RNA elements to initiate translation independent of 5-cap recognition of mRNA, particularly show efficient activity under disease stress that causes global canonical translation repression. Studies on distinct structural properties and interaction with translational factors have revealed the mechanisms and regulation of IRES-mediated translation. This allowed the application of IRES for cap-independent translation and dynamic modulation of protein expression in response to cell signals. In this review, we discuss the current platforms and emerging strategies for employing IRES-mediated translation towards novel RNA therapeutics.