Gene therapy for cystic fibrosis (CF) is a strategy that targets the genetic defect causing the disease. There are different gene therapy approaches. The most promising for CF are gene editing, using the CRISPR-Cas technique, and delivering CFTR messenger RNA (mRNA) to cells to produce a functional CFTR protein. In both cases, the systems must be delivered to the right type of cells, which for CF are lung epithelial cells.

The project aims to identify the most efficient delivery systems for gene therapy technologies. These systems must overcome both cellular barriers (i.e. the membrane) and extracellular barriers, such as the lung microenvironment, which in CF is difficult to penetrate due to thick mucus and chronic inflammation. Different delivery systems, based on viral particles or lipid nanoparticles, will be developed and tested. The project will also assess the best gene correction system, CRISPR-Cas or mRNA, to be delivered into the cells.

Gene correction and delivery systems will be tested in primary cells from people with CF with different mutations and in animal models to evaluate their effectiveness in the lungs. The project involves international researchers specializing in gene therapy, genome editing, delivery systems, and experimental CF models.

The final goal is to develop the best formulations to correct the genetic defect in CF, regardless of mutation type, and eventually create an inhalable treatment for people with CF.
The project started in early 2024 with a total budget of €1,870,207.50 for three years.

For information on how to support the project, contact fabio.cabianca@fibrosicisticaricerca.it.