Exosomes and miRNAs in disease pathogenesis and opportunities for molecular targeting

Exosomes/extracellular vesicles (EVs) are cell-derived mixed-populations of vesicles released by almost all cells into the intercellular microenvironment, ending up in the circulation. Exosomes contain proteins, RNAs and lipid molecules reflecting the status of the parental cell at the time of release, making them promising candidates for biomarker discovery. The contents of exosomes are protected by a lipid bilayer, leading to better stability of bio-macromolecules. Recent evidence suggests a novel role for exosomes as conveyors of information among cells and across tissues, through horizontal transfer of proteins, lipids, and nucleic acids. Exosomes have been the subject of numerous research in recent years; however, their roles still have to be identified in the pathogenesis of different diseases.

MicroRNAs (miRNAs) are small (18-25 nucleotide long) non-coding RNAs which play pivotal roles in the gene expression process and it is estimated that about one third of the human genome is controlled by miRNAs. miRNA regulatory processes have been found to influence many essential biological pathways, such as cellular development, proliferation, apoptosis, and cellular signaling. A great proportion of miRNAs has been reported to be associated with the exosome function of different biofluids.

The aim of this research was to elucidate the role of exosomes/EVs as well as miRNAs in the pathogenesis of different diseases, including alcoholic liver disease, hepatitis C, and cancer. This knowledge may lead to the development of novel molecular diagnostic approaches, as well as innovative drug delivery modalities for small RNA-targeted therapy. My research resulted in a) the establishment of new methods and approaches to the study of exosomes/EVs, as well as comparative literature on the efficacy of several isolation and characterization techniques. b) identification of the role of exosomes and miRNA-122 in the cross talk between hepatocytes and immune cells in alcoholic liver disease c) identification of the role of exosomes in HCV pathogenesis, including the potential of molecular therapies based on miRNA and exosome targeting in vitro and in vivo d) understanding the bio-distribution of exosomes and miRNA in an in vivo murine model and f) exploring the utility of miRNA and exosomes in biofluids in cancer biomarker discovery.