The Omnes Pro Uno (OPU) research group at Utrecht University aims to cure genetic diseases by detecting and correcting errors in DNA before irreversible damage occurs in the body. They want to optimise gene editing techniques and apply them in a safe and responsible manner.
Tailored treatment for genetic diseases
Every single day, babies are born in the Netherlands with a genetic disorder. More than 10,000 families in our country have one or more children with an inherited metabolic disease. These children often lack a protein that causes their cells not to absorb nutrients or break down waste products properly. At some stage in life, this leads to serious damage to organs such as the heart, the brain, or the nervous system. For the majority of these children, there is no effective treatment. As a result, they often die at a young age.
The Omnes Pro Uno (OPU) research group at Utrecht University has been doing everything possible for these children and their families for ten years. OPU’s mission is to cure patients with a genetic disease by detecting and correcting errors in DNA before irreversible damage occurs in the body. The five highly talented researchers have the expertise to optimise the gene editing techniques that are currently being developed at a rapid pace, and to apply them in a safe and responsible manner.
"The researchers have the expertise to optimise the gene editing techniques that are currently being developed at a rapid pace, and apply them responsibly"
OPU’s ambitious research has led to numerous groundbreaking discoveries in the past ten years. For example, the research group has succeeded in growing organoids – kinds of mini-organs – in the laboratory from various tissues of the human body such as the intestine, liver, brain and tumours. With these mini-organs, the researchers have both the complete genome and the characteristics of a patient’s organ for their purposes. This makes it possible to test new, often expensive treatments and genetic technologies on the organoids.
Thanks to the OPU research, an expensive treatment for patients with cystic fibrosis, for example, can now first be tested on intestinal organoids in the laboratory. If it works there, the insurer will reimburse the patient for the actual treatment. For cancer patients, too, different therapies can first be tried out on minitumours in the laboratory, after which the most successful one is then applied. The same is the case for promising treatments against SARS-Cov-2, which can be tested on organoids from the respiratory tract. These groundbreaking results have been widely recognised as evidenced by articles in numerous international publications and leading scientific journals, many prestigious awards and frequent invitations each year to give lectures worldwide.
OPU succeeded in being the first in the world to correct genetic errors in patients’ mini-organs using the latest genetic technologies. Now that this has been achieved, the team is ready for the next promising step: with the prize money from the Ammodo Science Award, OPU aims to be the first in the world to correct the genetic cause of diseases directly within the bodies of patients via the bloodstream, so that the disease does not have a chance to damage or affect the body adversely. The goal is to develop customised treatment for many different rare genetic diseases in an ethically responsible manner.
To achieve this, OPU must be able to optimise the ‘gene correction tool’ in such a way that it can be used not only in the laboratory, but also in the patient’s body. If this is successful, the next challenge will be to deliver the tool to the appropriate organs in the human body in order to correct genetic errors. The researchers expect that recent experience with mRNA vaccines will help them to use a similar technique to deliver the gene correction tool in patients. If they succeed, they intend to make this treatment available to as many genetic patients as possible.
"How far can we go with genetic techniques and how do we develop these techniques safely?"
Remarkably, the team is also conducting ethical research in parallel with their biomedical research, something that is often overlooked in technological innovations. Because of the major social impact of the research, ethical considerations are however crucial. How far can we go with genetic techniques and how do we develop these techniques safely? How can mini-organs be used responsibly? How can scientific research be brought to the aid of the patient in a rapid but safe way? These are some of the questions that constantly arise in the scientific work of the OPU researchers. The perspectives of stem cell biologists, clinicians, patients, policy makers and ethicists are indispensable to ensure the morally responsible application of genetic engineering. OPU therefore includes these perspectives in every phase of its research.
What makes the five-person OPU team so strong is that the researchers seemingly effortlessly integrate their various areas of expertise – from molecular genetics to biomedical technology and ethics – at all stages of their research. By joining forces, they are able to achieve their mission. The improvement of genetic techniques that the researchers envisage can also contribute to other forms of genetic research and new applications, for example in other diseases or in the food industry. The way in which OPU has managed to build a bridge between laboratory research and clinical practice is extraordinary and is making a revolutionary difference to the prospects of patients with serious hereditary disorders.
Ruben van Boxtel (1979) leads a research group at the Prinses Máxima Centre for Paediatric Oncology in Utrecht where he uses DNA research and bioinformatics to unravel causes of cancer. He studied Medical Biology at Radboud University Nijmegen and did his PhD research at the Hubrecht Institute (Utrecht). For his postdoctoral research he worked at UMC Utrecht and in 2015 as a visiting researcher at the Wellcome Sanger Institute in the UK. He received several prestigious grants, such as a NWO VIDI grant and an ERC Consolidator grant. In 2019, he was appointed as an Oncode researcher after a competitive open selection round.
Annelien Bredenoord (1979) is a professor, ethicist, administrator and supervisor. She studied Theology and Political Science (Leiden University) and obtained a PhD in Medical Ethics (Maastricht University). From 2008 to 2021, she was associate professor and professor of Ethics of Biomedical Innovation at UMC Utrecht. As department head and research leader she pioneered parallel ethical research for new biomedical technology. She received many prestigious grants including from Veni, KWF, Horizon, and ZonMw. She was also a member of the Young Academy of the KNAW. Since 2015, she has been a member of the Dutch Senate and as of 2019, she is party leader on behalf of D66. Since 2021, she has been rector magnificus at Erasmus University and professor of Ethics of Technologies at the Erasmus School of Philosophy.
Hans Clevers (1957) studied Biology and Medicine at Utrecht University where he also obtained his PhD, and has a postdoctoral qualification from Harvard University. He was Professor of Immunology from 1991 to 2002, and since 2002 of Molecular Genetics. He was also director of the Hubrecht Institute (2002-2012), president of the KNAW (2012-2015) and scientific director of the Princess Maxima Centre (2015-2019). He is a member of the KNAW, US National Academy of Sciences, Royal Society of London and the Académie des sciences. He has received many awards including the Breakthrough Prize in Life Sciences. He is Chevalier de la Légion d’honneur and Knight of the Order of the Dutch Lion.
Sabine Fuchs (1974) is a paediatrician of Metabolic Diseases and a researcher at UMC Utrecht. She graduated cum laude in Pharmacy and Medicine from Utrecht University. She combined her paediatric training with PhD research into metabolic diseases and her specialisation as a metabolic paediatrician with setting up a research unit at the RMCU (Hubrecht Institute). She received several prestigious grants including ZonMW AGIKO, ZonMW Clinical Fellows and ERC Starting Grant, and awards such as the Elisabeth von Freyburg medal. To stimulate translational research, she is active in the EUREKA certificate programme, the Utrecht Translational Medicine Summer School and Training Upcoming Leaders In Paediatric Science (TULIPS).
Edward Nieuwenhuis (1965) is professor of paediatrics and researcher at the UMC Utrecht and professor of Biomedical and Life Sciences at University College Roosevelt (UCR). He studied medicine at the University of Amsterdam and is professor of paediatrics at the Wilhemina Children’s Hospital and paediatric gastroenterologist at the Sophia Children’s Hospital. He conducted molecular immunology research in Utrecht and Boston and obtained his PhD in 2002. From 2009 to 2019, he directed the Wilhemina Children’s Hospital. In 2007 he became a VIDI laureate (ZonMW) and in 2020 a Knight of the Order of the Dutch Lion.
