Researchers at KU Leuven have taken an important step in the research and treatment of cystic fibrosis. For the first time, they have succeeded in precisely repairing the mutations in the gene that cause cystic fibrosis in human airway cells.
Cystic fibrosis or cystic fibrosis disease is a congenital condition in which a tough mucus in the lungs and intestines causes blockages. Patients fight a daily battle to control their symptoms, with medication, aerosol and kine, and sometimes even with a lung transplant. In the past, mucous membrane patients died as children; Nowadays the median life expectancy of a baby with cystic fibrosis is 49 years and the quality of life is much higher. However, curing the disease is still not possible.
“The cause of cystic fibrosis lies in mutations of one gene and that makes the avenue of gene therapy interesting,” says Professor Marianne Carlon, who leads the cystic fibrosis research at KU Leuven. “In classical gene therapy, the correct gene is added – next to the mutated gene. With the new gene therapy, a mutation is cut out and replaced. The original error is corrected, making the gene completely the same as in healthy people. So you can really speak of a genetic change.”
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The researchers used the ‘prime editing’ technique, a way to modify DNA very precisely, which is based on the well-known CRISPR method. “We succeeded in very precisely adapting mutations in the CFTR gene to the correct variant,” explains doctoral researcher Mattijs Bulcaen. “For the first time, we were able to ‘cure’ mucosal mucosa in human airway cells.”
The study has now been published in the scientific journal Cell Reports Medicine.
To validate their genetic modifications in the cells, the team developed ‘DETECTOR’, an AI-driven technology that analyzes microscopy data from organioids. Organoids are mini-organs that are grown in the lab from biopsies obtained from mucous membrane patients. By releasing DETECTOR on the organoids, it was possible to determine which cells were still ‘sick’ and showed muco-properties, and in which cells the prime editing had worked and were therefore muco-free.
Milestone
The next challenge is the leap from the petri dish to the patient. “To date, successful gene editing treatments have mainly been used for blood diseases because stem cells can be isolated from the blood or bone marrow, modified outside the body and then reintroduced,” Carlon explains. “The approval at the end of 2023 of the first ever CRISPR drug, ‘Casgevy’ for the blood disease sickle cell anemia, is an important milestone that paves the way to develop CRISPR therapies for other diseases in the future. Although there is a lot of research into this, the development of such a therapy in lung diseases is more difficult for various reasons – just the fact that we are talking about the surface of a tennis court.”
