In 1989, the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene was discovered, whose malfunction leads to the disorder Cystic Fibrosis (CF). CF is the most frequent hereditary disease found in the Caucasian population. Several organ systems, such as the respiratory tract, the digestive system and the reproductive organs, are affected. Particularly pronounced are the symptoms in the lung, in which viscous mucus collects, offering an optimum nutrient medium for bacteria. Patients with CF suffer accordingly, often with severe infections, inflammation of the lungs and an increasing loss of lung function. Since the condition is caused by a single gene, there have already been numerous attempts to find an appropriate gene therapy, however with moderate success up to now.
In the current study, the scientists have attempted to introduce the healthy CFTR gene into the mice that have a Cftr mutation using nanoparticles. To do this, a direct application into the airways was selected and the integration of the gene checked using a so-called reporter (in this case the luciferase gene, which also causes glow-worms to glow). Using a special camera, they were able to check the light signal of the reporter in the lungs of the mice and thus verify a stable integration of the target gene in the DNA of the treated animals. The non-viral vector (gene shuttle) displayed practically no toxic effects here, did not lead to increased signs of inflammation in the lungs of the experimental animals and showed a secure integration pattern. The nanoparticles administered are therefore considered to be a very promising use of an innovative gene therapy for cystic fibrosis.
Implementation of the study within the framework of a cooperation project with Prof. Joseph Rosenecker’s team at the LMU Munich was only possible thanks to an outstanding cooperation with a number of institutes on the MHH campus.