Oral Presentation Australasian Extracellular Vesicles Conference 2020

Omics characterization of mimetic-nanovesicles reveals their relevance as a therapeutic modality (#28)

Amirmohammad Nasiri Kenari 1 , Kenneth Kastaniegaard 2 , Mitch Shambrook 1 , David Greening 1 , Allan Stensballe 2 , Lesley Cheng 1 , Andrew Hill 1
  1. Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, VIC, Australia
  2. Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg , Denmark

Using extracellular vesicles (EVs) as a therapeutic modality is currently facing challenges such as the insufficient release of EVs, their heterogeneity and reproducibility of isolation, and engineering with therapeutic cargo. To overcome some of these issues, several methodologies have been developed to boost or mimic EVs therapeutic potential. EV mimetic nanovesicles (M-NVs) can be generated using the cell as an initial material for the generation of nanovesicles (by top down method) providing advantages such as, reproducibility, large scale production, uniformity, cost effectiveness and a simple purification method. Although several studies have shown that M-NVs have similar morphology, size and therapeutic potential to exosomes (endosomally derived vesicles with higher expression of tetraspanin proteins such CD63, CD81, and CD9), comprehensive characterization and to what extent these M-NVs components mimics exosomes remain elusive. In this study, we comprehensively characterized and compared the proteomic and transcriptomic profile of M-NVs to exosomes, which provide key insights into the cargoes carried by M-NVs. Furthermore, our study highlighted differences in protein post-translational modifications among M-NVs, as being distinct from exosomes. The RNA cargo of M-NVs is similar to that of the parental cell in comparison to exosomes. We also found that M-NVs could be useful for packaging proteins or RNA which are globally enriched in cells. Indeed, this may overcome the challenges involved in selective packaging of therapeutic into exosomes. In summary, we have revealed omics of M-NVs in comparison to exosomes and parental cell and highlighting M-NVs potential as therapeutic delivery system.