ENGINEERINGNET.BE – Cystic fibrosis or cystic fibrosis is a congenital condition in which tough mucus in the lungs and intestines causes blockages.
“The cause lies in mutations of one gene. That makes gene therapy interesting,” says Professor Marianne Carlon of KU Leuven.
“With 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, so that the gene is completely the same as in healthy people.”
The researchers use the prime editing technique for this: a way to modify DNA very precisely, based on the CRISPR method.
“We managed to accurately adjust 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.”
To validate their genetic adjustments in the cells, the team developed the new tool DETECTOR. This AI-driven technology analyzes microscopy data from organoids to determine which cells are still diseased and in which cells the prime editing has worked and are therefore muco-free.
“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 CRISPR drug for the blood disease sickle cell anemia is an important milestone. This paves the way to develop CRISPR therapies for other diseases in the future. In lung diseases, the development of such a therapy is more difficult for various reasons, including the large total surface area of the lungs.”
Bulcaen: “The fact that we can specifically modify genes in human cells and in replica organs in the lab without collateral damage is a huge step forward. Now the most important research question is how we can apply this technology in the body itself.”
This research was carried out in collaboration with the Italian University of Trento and the French INSERM. The Belgian Fund for Scientific Research, the Belgian Mucosity Association, King Baudouin Foundation and Emilys Entourage contributed financially to this:
In the image above: left organoids before treatment, right organoids after prime editing treatment
