Delivering therapeutic RNA into the brain using extracellular vesicles

RNA science has experienced a surge, particularly its application to vaccine and therapeutic development. Delivery of RNA molecules into the brain remains one of the biggest therapeutic challenges with the blood-brain barrier excluding most drug-delivery modalities such as lipid nanoparticles. As RNA molecules are predisposed to degradation, harnessing its potential as a therapeutic agent requires protection during delivery into target cells. Several solutions have been offered to protect RNA molecules from degradation, with extracellular vesicles (EVs) garnering attention as naturally occurring nanoparticles released by cells, holding promise as carriers for RNA molecules. These EVs, which offer inherent protection to their cargo and have shown promise in efficiently and safely delivering RNA therapeutics present a promising avenue for advancing RNA-based therapeutics in combating various diseases. Here, we review this fast-developing field looking at the range of delivery strategies developed for RNA/EV brain delivery. We summarize the major issues with conventional RNA delivery techniques while emphasizing the potential benefits of EV-based treatments and suggest promising ways forward to progress the field so that we may realize the promise of delivering therapeutic RNA molecules in EVs as potential treatments for neurological disorders.