Explore how cells send RNAs to each other via exosomes and how to utilize this process for therapeutic purposes

Background: Extracellular vesicles (EVs) are a heterogeneous population of nano- and micro-sized vesicles, including microvesicles and exosomes that are secreted by almost every cell type studied so far.

EVs are detectable in many, perhaps all, biological fluids.Our key finding: We discovered, for the first time, that cells send RNA-messages to each other by packing them into exosomes (Valadi H. et al. Nature Cell Biology; cited > 5500 times).

Aim: The goal of this project is to understand how cells transmit RNA-molecules to each other via exosomes, and how to utilize this process for therapeutic purposes.

Specifically, we aim to (a) elucidate the cellular mechanism by which a group of cytosolic RNAs is sorted into exosomes, (b) define how mRNAs from early endosomes are translocated into exosomes (insertion of therapeutic mRNA into exosomes), and (c) explore the potential of using exosomes for in vivo mRNA-delivery to heart tissue, in order to treat tissue damages.

Preliminary results: Recently, we discovered that there is a linkage between endosomal escape of mRNA and loading into exosomes (Maugeri M. et al. Nature Communication, 2019).

More importantly, these exosomes could protect the mRNA during in vivo delivery and cause the production of a human protein (hEPO) in treated mice.Importance: Understanding the process of cell signaling via exosomes will have a strong impact on the knowledge of cell communication as well as on the emerging field of RNA-based therapeutics.