Targeted epigenetic reprogramming, or ‘epigenetic editing’, is an innovative technology that can modify the behaviour of genes, without causing a change in the DNA itself. According to researcher Pernette Verschure, it has incredibly wide-ranging applications: from more effective cancer treatment to immune therapy and from skin care to bio-engineering plants to withstand climate change. Find out about Verschure’s new research project at Amsterdam Science Park, where she is looking forward to tapping into the park’s wealth of scientific and digital expertise.
Verschure describes the epigenome as “a layer on top of the DNA sequence,” which affects how the DNA sequence is instructed to programme the cells in our body. “It gives instructions as to which genes should be turned on or turned off, so that each cell type can perform its specialised function in the tissues and organs of the body.” The epigenetic layer is flexible and affected by both environment and behaviour. Many diseases are related to changes in gene expression caused by epigenetic dysregulation, so reprogramming the epigenome has the potential to deliver new healthcare interventions. The possibilities this opens up, says Verschure, are “sky high.”
The epigenetic composition of the genome is driven by chemical modifications to the DNA, written and erased by epigenetic enzymes. “And these are, in principle, reversible reactions,” says Verschure. This doesn’t only mean that epigenetic changes causing diseases can be reversed. It also means that doing so will not change the DNA sequence itself, thus the process of epigenetic editing has fewer ethical considerations than are associated with genome engineering.
Pernette Verschure, Professor of Functional Epigenome Dynamics
“Epigenetic regulation processes work in a similar way in different organisms so there are a wide range of potential applications
Verschure leads a nation-wide consortium, including international partners, that has received a €2.5 million grant from the NWO KIC Key Technology call to develop sustained epigenetic editing as a key technology, and to actively engage society and industry in this process. The Science Park’s cross-sector collaborative approach makes it an ideal base for this. Verschure’s project, called Epi-Guide-Edit, combines fundamental scientific research with medical, biotechnological, industrial and societal applications. It brings together an interdisciplinary team aiming to deliver what she calls “tools and rules for sustained epigenetic reprogramming.”
Many different partners are involved. “We have academic institutes, medical centres and industry partners on board,” says Verschure, “and also Universities of Applied Sciences and societal partners.” While the fundamental research is focusing on the mechanisms of epigenetic reprogramming, she says that the industry partners involved are interested in “being at the forefront of getting this knowledge and using it for their applications.”
Epigenetic drugs already exist and are being used in limited clinical settings and in clinical trials but, says Verschure, “they act on all the genes at the same time. They have various kinds of side effects that you don’t want. They’re toxic. You’re wielding a hammer.” Epigenetic editing, on the other hand, can target the epigenome of a specific gene. It’s also different from genome editing, which affects the DNA itself and introduces permanent genetic modification. Reprogramming the epigenome is, in principle, flexible and reversible, while inducing sustained changes in gene expression.
Pernette Verschure, Professor of Functional Epigenome Dynamics
“Anti-ageing skincare, drug screening systems, bio-engineering plants, immune therapy. All are new opportunities
One of the advantages for businesses looking to apply epigenetic reprogramming is that epigenetic regulation processes are very uniform, Verschure explains. As they work in a similar way in different organisms, there are a wide range of potential applications. The project focuses on breast cancer, skin ageing, immune cells and plants. “There is a lot of interest in immune therapy, with work going on to change the T cells and make them better able to attack cancer cells,” she says. “Our work with skin cells and healthy ageing is very interesting for Unilever, which is focused on all kinds of skin and hair treatments and conditions affecting the oral cavity. Bristol Myers Squibb is interested in creating preclinical systems for drug screening and in breast cancer research, and plant-breeding companies are interested in bio-engineering their tomato plants, for instance, to survive climate change.” Partnerships with industry are also beneficial for the researchers, says Verschure. “Windows are opened to new opportunities and datasets that otherwise we would have no knowledge of.”
Along with the benefits, there are some challenges. “Scientists like to talk to each other about everything, because then we get a lot of input – but that could harm the collaboration with industrial partners. It’s less open; we have to look at disclosure and carefully protect confidentiality agreements”.
Still, interdisciplinarity and teaming up with others to exchange knowledge are key to achieving results, says Verschure. The Amsterdam Science Park is an ideal location for encouraging such collaborations, and the wealth of expertise in digital innovation on offer is of particular interest to Verschure and her scientific team. “Artificial intelligence is booming at the park. There’s Lab 42. There’s innovation on digital sciences, computer data, big data, all these things. And that is very interesting for us to team up with. We can do experiments – although they’re very expensive – but we can also learn from existing data, and computer analysis gives us a lot of information, so this is something we want to go into.”
The third element of the consortium is the involvement of societal partners. “We consider them to be very important, because if you are developing a new technology, you need to consider upfront what the public thinks of it and whether they would accept it. We want to have these discussions right from the start.” The project is working closely with the Rathenau Institute, a Dutch organisation for technology assessment. The Institute will be leading focus group discussions with the public to gauge sentiment around the technology. Verschure believes open discussion is essential for gaining acceptance. “In the beginning, we thought we just have to explain to people what we’re doing. But that’s not enough. You have to hear their voices – understand how the public thinks and if they think we should do things differently. We do try to really put this on the agenda. We’re not developing the technology for nothing: it’s something that is going to end up in society.”
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