Therapeutic potential of RNA-enriched extracellular vesicles: The next generation in RNA delivery via biogenic nanoparticles.

Exosomes are extracellular vesicles (EVs) (∼50-150 nm) that have emerged as promising vehicles for therapeutic applications and drug delivery. These membrane-bound particles, released by all actively dividing cells, have the ability to transfer effector molecules, including proteins, RNA, and even DNA, from donor cells to recipient cells, thereby modulating cellular responses. RNA-based therapeutics, including microRNAs, messenger RNAs, long non-coding RNAs, and circular RNAs, hold great potential in controlling gene expression and treating a spectrum of medical conditions. RNAs encapsulated in EVs are protected from extracellular degradation, making them attractive for therapeutic applications. Understanding the intricate biology of cargo loading and transfer within EVs is pivotal to unlocking their therapeutic potential. This review discusses the biogenesis and classification of EVs, methods for loading RNA into EVs, their advantages as drug carriers over synthetic-lipid-based systems, and the potential applications in treating neurodegenerative diseases, cancer, and viral infections. Notably, EVs show promise in delivering RNA cargo across the blood-brain barrier and targeting tumor cells, offering a safe and effective approach to RNA-based therapy in these contexts.

Extracellular vesicles: The next generation in gene therapy delivery.

Extracellular vesicles (EVs) are esteemed as a promising delivery vehicle for various genetic therapeutics. They are relatively inert, non-immunogenic, biodegradable, and biocompatible. At least in rodents, they can even transit challenging bodily hurdles such as the blood-brain barrier. Constitutively shed by all cells and with the potential to interact specifically with neighboring and distant targets, EVs can be engineered to carry and deliver therapeutic molecules such as proteins and RNAs. EVs are thus emerging as an elegant in vivo gene therapy vector. Deeper understanding of basic EV biology-including cellular production, EV loading, systemic distribution, and cell delivery-is still needed for effective harnessing of these endogenous cellular nanoparticles as next-generation nanodelivery tools. However, even a perfect EV product will be challenging to produce at clinical scale. In this regard, we propose that vector transduction technologies can be used to convert cells either ex vivo or directly in vivo into EV factories for stable, safe modulation of gene expression and function. Here, we extrapolate from the current EV state of the art to a bright potential future using EVs to treat genetic diseases that are refractory to current therapeutics.