In the latest episode of the Genetics Unzipped podcast, sponsored by Lonza, we’re unpacking one of the hottest new areas of research for both diagnosing and treating diseases, and that’s exosomes.
Once thought to be little more than ‘dust’, exosomes are tiny biological mailbags that travel around the body, as Kat Arney hears from Rossella Crescitelli. Sally Le Page talks to Doug Williams to learn how exosomes can be used to reduce the toxicity of cancer treatments by targeting drugs directly to tumours. And Davide Zocco tells us how they are scaling up manufacturing to take exosome treatments from the lab to clinics.
Molecular mailbags
To put it simply, exosomes are tiny bags of ‘stuff’ produced by cells that can travel around the body. They contain a mixture of the same kinds of things that you’d find in a regular cell – DNA, RNA, proteins, fats and other chemicals – all wrapped up in the same kind of membrane that surrounds our cells, known as a lipid bilayer. You can imagine them almost like a sample from inside the cell, wrapped up neatly in a biological mailbag and posted out into the world of the body.
“Exosomes are different from other kinds of particles,” explains exosome researcher, Rossella Crescitelli. “The magic thing about them is that they are recognised as ‘self’ by cells, so they can last a long time circulating around the body and can even cross the blood-brain barrier.”
But these exosomes aren’t just floating around in the bloodstream randomly. As they’re being created, the cell adds specific instructions for where the exosome should go, and which cells it should bind to.
Taming the toxicity of chemotherapy
The ability of exosomes to target specific cell types has piqued the interest of researchers studying drug delivery systems, such as Doug Williams.
“How can we take this naturally occurring system in the body that’s used for cells to talk to each other and figure out a way to put drugs on these exosomes and get them delivered where we want them?” he asks.
Delivering a drug to the right place can be the difference between being able to treat a cancer or not. The molecule used to target cutaneous T-cell lymphoma works well at reducing the size of tumours. However, it hasn’t been developed as a viable drug because when it’s given to patients it affects all the cells in the body, not just the cancerous ones, causing overwhelming side effects.
“The inability to control the toxicity was the Achilles’ heel for that particular molecule,” says Williams. “By attaching the molecule to the surface of an exosome, we make sure the drug stays in the tumour so we get all of the beneficial aspects of the drug locally without the side effects.”
From the Petri dish to patients
With exosomes showing such promise in treating difficult diseases, it’s important that scientists develop efficient processes for manufacturing them at scale, which is the focus of Davide Zocco’s work.
“We have big vats containing cells that produce the exosomes we want,” Zocco describes. “To get pure exosomes, we need to filter out all of the cell debris and then check that the exosomes haven’t been damaged.”
Although the many stages in the purification process are vital in ensuring a safe product, exosomes can be lost at each stage. “Only 30% of exosomes that go through the process end up being purified,” he explains.
However, Zocco is optimistic for the future of exosome therapies. “Hopefully we will be able to meet the demand for exosomes within three to five years”.
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Genetics Unzipped is the podcast from the UK Genetics Society, presented by award-winning science communicator Dr Kat Arney and produced by First Create the Media. Follow Genetics Unzipped on Twitter @geneticsunzip, and the Genetics Society at @GenSocUK
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