OBSERVE Project Research Roles

Researchers in the OBSERVE project are investigating several issues around EVs, with the aim of eventually using them to deliver RNA therapeutics. We spoke to Diego Aguilar Rodriguez and Willemijn de Voogt , PhD students at UMC Utrecht, about their role in the project, the methods they’re using, and the wider possibilities of RNA therapeutics.

EU Researcher: Could I ask you both about your respective roles in the project?

Willemijn de Voogt: My role is on the fundamental part of the project. I’m trying to unravel the biology behind EVs – how are they taken up? Which proteins or RNAs are involved in functional EV transfer? I’m looking at the pathways of intra-cellular trafficking, and the pathways underlying the transfer of RNA molecules.

Diego Aguilar Rodriguez: I’m focused more on the potential therapeutic applications of EVs, with the goal of developing novel therapeutic tools to deliver mRNA. We’re looking to harness the properties of these EVs and trying to apply them in drug delivery. We’re trying to learn about these EVs and the potential benefits of their use in terms of things like uptake, targeting and preferential accumulation.

EUR: Could you then look to bring these attributes to synthetic drug delivery systems?

DAR: This is what we’re trying to do. Both EVs and synthetic drug delivery systems have limitations - we’re trying to get the best of both worlds.

EUR: How does the relationship between basic and applied research work? Do you need to collaborate quite closely?

WdV: Not yet, as the project is still at quite an early stage, but hopefully more so later on. For instance, if I find that certain proteins are essential for uptake or functional delivery in a certain cell type, then potentially Diego can design hybrids that contain specifically these proteins.

EUR: How will you use microfluidic mixing to create hybrids?

DAR: One of the phases is the organic phase, with synthetic lipids. In the aqueous phase we’ll have EVs with the therapeutic reagent, in this case mRNA. Then we will hybridise them with a microfluidic chip, then at the end we purify the sample.

EUR: Do you see wider potential in RNA therapeutics?

Pieter Vader is Associate Professor at CDL Research and at the Department of Experimental Cardiology at the University Medical Center Utrecht. His main research interests are in the field of therapeutic applications of extracellular vesicles, including unraveling the mechanisms underlying extracellular vesicle-mediated cargo transfer. In 2021, Pieter was award the Prix Galien Research Award for his work on drug delivery.

WdV: Very much so, we’ve seen the therapeutic potential of RNAs in recent times, for example with the development of vaccines against Covid-19. By exploiting these delivery vehicles, we can look to target specific diseases in multiple ways, such as by trying to express certain genes or knock down certain genes.