RNA and Protein Delivery by Cell-Secreted and Bioengineered Extracellular Vesicles

Extracellular vesicles (EVs) are carriers of biological signals through export and delivery of RNAs and proteins. Of increasing interest is the use of EVs as a platform for delivery of biomolecules. Preclinical studies have effectively used EVs to treat a number of diseases. Uniquely, endogenous machinery within cells can be manipulated in order to produce desirable loading of cargo within secreted EVs. In order to inform the development of such approaches, an understanding of the cellular mechanisms by which cargo is sorted to EVs is required. Here, the current knowledge of cargo sorting within EVs is reviewed. Here is given an overview of recent bioengineering approaches that leverage these advances. Methods of externally manipulating EV cargo are also discussed. Finally, a perspective on the current challenges of EVs as a drug delivery platform is offered. It is proposed that standardized bioengineering methods for therapeutic EV preparation will be required to create a well-defined clinical product.