RNA-loaded exosomes: the drug carriers of the future?

Pieter Vader, associate professor at UMC Utrecht, conducts extensive research into exosomes, the body's own membrane vesicles, for the delivery of RNA medicines. Exosomes are promising and investments in new research are growing rapidly worldwide. His colleague Sander Kooijmans will give a lecture on this subject during the Life Science event on April 5.

By: Dimitri Reijerman

During the corona pandemic, a lot of attention has been paid to mRNA vaccines, such as the vaccines from BioNTech/Pfizer and Moderna. But getting RNA to the right place requires a lot of work. Father explains the role of exosomes in this: “We have heard a lot about mRNA medicines and vaccines over the past year during the Covid outbreak. But with RNA medicines we can not only switch genes on but also switch them off. And also think of the CRISPR/Cas development with which we can change genes. These are all RNA medicines and therefore have enormous potential, but something has to be done with them. You cannot simply swallow or inject them, because then the RNA is immediately broken down. The RNA must therefore be packaged in nanoparticles. These particles must ensure that the RNA can reach a diseased cell at the right place in the body. The RNA is therefore protected during its journey through the body thanks to the nanoparticles.”

He continues: “There are more people working on RNA medicines and nanoparticle delivery systems. Many researchers are developing synthetic nanoparticles that are made in the lab. I also do some research into that, but the major disadvantage is that these particles are foreign to the body and you can get an immunogenic reaction. In the case of vaccines this is not so bad, but in many other applications you do not want an immunogenic reaction.”

Body's own blisters

That's where the body's own blisters come into play. “About ten years ago it was discovered that similar nanoparticles exist in our own bodies,” says Vader. “These endogenous nanoparticles, which we call exosomes, have the function in our body of transferring biological information from one cell to another cell, including RNA. So what we're studying is whether we can use those nanoparticles, which we find naturally in our bodies, to deliver RNA drugs. We try to isolate those exosomes, load them with RNA medicines and perhaps improve them a bit and then treat the patient.”

But the research design is broader: “On the other hand, we study them very closely because those vesicles can get RNA into cells very efficiently. But the question is: how exactly do they do that? And can we imitate or use that? These are the two pillars we are working on in our lab.”

Despite the promise of RNA medicines delivered into the body via exosomes, much remains to be done, the researcher says: “The research is still partly in its infancy. There are no concrete applications in the clinic yet, but you can now see the first clinical studies being started. And things are going very fast in the field: research is growing exponentially every year. There is also a lot of attention from the industry and a lot of money is being pumped in.”

To apply

The application possibilities are also endless: “It is used for all kinds of contexts. When I look at the therapy angle, most applications are in regenerative medicine. For example, we know that exosomes derived from stem cells have similar properties to the stem cells themselves. So they have very beneficial regenerative properties. After an infarction or damage to the kidneys, these blisters can automatically promote new blood vessels and repair damage to cells. These exosomes naturally want to help repair the body. This field of research is also the most advanced. Neurodisorders are also examined. There are indications that exosomes can cross the blood/brain barrier, something that almost no synthetic particle can do. Research is also being done in the cancer research field.”

When implementing the concept of a natural drug carrier, there are two ways this can be achieved, says Vader: “What we want is to get the drug into the exosome. An exosome is actually a ball of fat. We want to get the RNA in there. The first way is to use a cell's machinery to put the RNA into an exosome. To this end, we try to manipulate cells in such a way that they serve as a kind of factory that makes RNA medicines and inserts them into the exosomes themselves. With genetic engineering we can ensure that this process happens efficiently. Another way is to open the exosomes once they have been isolated, put the RNA in them and then close them again. But both methods are still difficult to implement and a lot of attention needs to be paid to them.”

Immune privilege

According to Vader, it is not yet entirely clear whether exosomes from person A also work for person B. “That depends, among other things, on which body cell the exosomes come from. Certain cells have an 'immune privilege' which means they will hardly show any defense between people. You also see this with certain stem cells if you match people well. But whether this will apply to all exosomes remains to be further investigated.”

Due to the promising properties of exosomes, research continues to grow, says the UMC Utrecht researcher: “The Netherlands is traditionally a very big player. The first discoveries were in the Netherlands. Utrecht in particular was and is a capitol in that area. But the research field has grown so much that a lot of research is being done and investments are being made, especially in America and China. So those countries are making a lot of progress.”

Would you like to attend Sander Kooijmans' lecture? Register for the Life Science Event free of charge via the website.