Delivering on the potential of RNA therapeutics
RNA therapeutics hold great potential as a means of treating a range of diseases, yet they are also immunogenic and it is difficult to transport these molecules to specific locations in the body. We spoke to Dr Pieter Vader, Diego Aguilar Rodriguez and Willemijn de Voogt about the work of the OBSERVE project in developing extracellular vesicle-based systems to deliver RNA drugs into the body. The potential of
RNA therapeutics is enormous, with researchers investigating possible applications in vaccine development, cancer treatment and several other areas of medicine, yet RNAs are also difficult molecules to work with. These molecules are fragile and can be degraded by various different enzymes, while there are also further issues to overcome before they can be applied more widely. “They are immunogenic, while they are also large and negatively charged, so they cannot spontaneously enter cells, which is necessary for them to perform their function,” says Dr Pieter Vader, Associate Professor in CDL Research and the Department of Experimental Cardiology at the University Medical Center Utrecht. As the Principal Investigator of the OBSERVE project, in which he is working together with PhD students Diego Aguilar Rodriguez and Willemijn de Voogt, Dr Vader is investigating the possibility of using extracellular vesicles (EVs) as a way to deliver RNA therapeutics and help overcome the issues which are currently limiting their application. “These
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EVs are vesicles that are secreted by the cell, towards the extracellular milieu,” he outlines.
Extracellular communication These EVs are thought to have a variety of roles, with Dr Vader primarily interested in their role in intercellular communication. Some EVs are able to deliver content including proteins, RNAs and other small molecules in a
it?” he explains. A tool based on the CRISPRCas9 machinery is being used in the project to study EV-mediated RNA delivery on the single cell level. “With this tool we can see which cells in a dish or an organoid have taken up RNA via our vesicles,” continues Dr Vader. “We can then try comparing different types of vesicles in terms of which deliver most efficiently. We can perhaps then modify them
We’re studying naturally occurring extracellular vesicles – we study what they carry, how they carry it, as well as how they deliver it. We’re really trying to map that – which vesicles can deliver RNA and how do they do it? functional manner to other cells, a topic that Dr Vader and his colleagues in the project are investigating. “We’re studying naturally occurring EVs – we study what they carry, how they carry it, as well as how they deliver it. We’re really trying to map that – which vesicles can deliver RNA and how do they do
a little bit and ask the question; does their delivery capacity improve?” This is an important issue in terms of using these vesicles therapeutically, an issue high on the project’s agenda. Researchers are using naturally-occurring vesicles, but certain changes are necessary in order to
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