Extrahepatic delivery of RNA to immune cells

Immune cells play a pivotal role in all aspects of human health, ranging from protection against external pathogens to involvement in autoimmune diseases and cancer. RNA therapeutics hold great promise as the next generation of therapeutics for the treatment of a wide array of diseases. Therefore, there are many efforts to develop specific nano-vehicles for the delivery of therapeutic RNA molecules to immune cells and their subsets. This effort requires technological solutions to decrease side effects, to target the desired immune cells subtype, to avoid accumulation in the liver, to release the payload from the endosome, and to improve effectiveness. Over the last 15years, a variety of RNA delivery systems have been designed to target immune cells. In this chapter, we describe the various RNA-delivery systems, conjugates, and nanoparticles that demonstrated the most effective immune cell targeting in vivo. Furthermore, we discuss the advantages and drawbacks of each approach. Ultimately, we critically assess the current achievements of each approach and share insights to optimally match RNA-delivery platforms to indication.