Virus-modified exosomes for targeted RNA delivery; a new approach in nanomedicine

Abstract

A major goal in biomedical research is to clinically reverse the cause of disease rather than treating the symptoms. Gene therapy has the potential to meet this goal and the discovery of RNA interference (RNAi) has lead to a new class of highly selective therapeutics. However, initial enthusiasm is reduced due to safety concerns associated with virus-based delivery vectors that are used for in vivo delivery. Viral vectors for siRNA delivery into target cells are used because of their high target specificity and delivery efficacy (endosomal escape). Recent discoveries suggest that a specialized form of nano-sized lipid vesicles called exosomes can incorporate and transport functional RNAs into target cells and may serve as an attractive alternative. Evidence is accumulating that most pluricellular organisms sustain exosome-based communications via inter-cellular exchange of mRNA and miRNAs between cells. We discovered that viruses have found ways to exploit this communication pathway and we argue here that adaptations of exosomes imposed by viruses maybe exploited for superior delivery of RNA in vivo. We discuss recent discoveries in exosome biogenesis their physical properties, targeting and delivery strategies and how the knowledge of exosome production in virus infected cells could propel their entry into clinical settings.