Cystic fibrosis is among the most common, known and studied genetic diseases. It affects over 100,000 people worldwide and reduces life expectancy mainly as it causes lung and respiratory problems. Over the years, scientific research has led to the development of several pharmacological therapies for this disease. Now, a study coordinated by the University of Trento marks a turning point, as it identified a gene therapy for individuals with cystic fibrosis caused by a specific mutation and for whom there was no treatment available until now. They are about 10% of all those with the disease. The results open up further prospects because they could lead to a definitive cure for patients with cystic fibrosis who are currently dependent on drugs.
An article that has just been published in Science Translational Medicine provides more details. The work was coordinated by Anna Cereseto in collaboration with Alessandro Umbach of the University of Trento, co-corresponding authors.
The paper focuses on the 1717-1G >A mutation and on the development of an mRNA-based strategy that makes it possible to effectively and permanently correct the mutation responsible for cystic fibrosis that does not respond to some of the available pharmacological therapies.
"We have developed a gene therapy to repair a mutation that causes cystic fibrosis, for which no cure has been found so far. The individuals with the mutation – 10% of those with the disease – do not produce the protein (CFTR), which transports chloride and bicarbonate ions across the surface of the lung epithelium, where it regulates mucus hydration and cleansing. Cystic fibrosis is a multi-organ disease that affects different parts of the body, with lung disease being the primary cause of mortality," explains Anna Cereseto of the Department of Cellular, Computational and Integrative Biology of the University of Trento.
She continued: "We have developed a genome editing technology based on messenger RNA. This strategy makes it possible to effectively and permanently correct the DNA mutation that is responsible for cystic fibrosis and does not respond to current pharmacological therapies. We repair that single 'defective brick' within the CFTR gene, to restore the production of the protein that regulates gas exchange and immune defense in the lungs."
She emphasizes: "With advanced gene editing technology that works with extreme precision, we were able to modify the sequence of individual DNA letters and replace pathogenic adenine (the 'defective brick') with guanine and restore the information needed to produce the protein. The therapy is administered to the cells in the form of messenger RNA. The gene editor produces a permanent correction of the genetic defect and is then expelled from the body."
The therapy was tested in this preclinical research phase. "To verify the effectiveness of the functional correction, we collaborated with the Telethon Institute of Genetics and Medicine (Tigem) of Pozzuoli, Naples, for the cells of the lung epithelium, the tissue that lines the airways and alveoli of patients. And with KU Leuven, in Belgium, for intestinal organoids, miniature three-dimensional models of the intestine, derived from patients' cells."
The results of the study also open up new prospects for the treatment for patients with cystic fibrosis who are currently dependent on drugs.
"The bottleneck now is to find systems to deliver this therapy into the tissue of the lung epithelium. In this more in-depth study we have the support of Fondazione per la ricerca sulla fibrosi cistica (Foundation for research on cystic fibrosis) through the strategic project GenDel-CF. The goal is to develop delivery systems for gene therapy technologies and to develop a treatment that can be administered by inhalation in the future."
Science Translational Medicine
Experimental study
Cells
Functional correction of the untreatable CFTR 1717-1G>A mutation through mRNA- and sgRNA-optimized base editing
22-Apr-2026