Viral vector technology as a gene therapeutic tool in search for a cure for cystic fibrosis.

Gene therapy theoretically offers one treatment for all the different CFTR mutations in cystic fibrosis (CF) patients, in contrast to small molecules that can only correct specific mutations. Viral vector mediated gene is described as being the most efficient method for the transfer of genetic material due to the fact that it exploits the naturally occurring ability of viruses to persist in a host cell. Our research group has extensive expertise in the biotechnological aspects of viral vector technology. We want to investigate the use of neonatal or even fetal gene therapy for CF, as treatment could be started before irreversible organ damage occurs. We will perform perinatal gene therapy experiments in the CF mouse model and monitor a potential restoration of CFTR function by nasal potential difference measurements. Appropriate CF cell lines are indispensable when screening for new treatments. A recently published functional CFTR assay using intestinal organoids provides a novel and sensitive tool to measure CFTR channel activity. We will optimize viral vector mediated transduction of organoid cultures so these organoids can be used as a diagnostic tool to evaluate the efficacy of CFTR gene transfer vectors in vitro before applying them in CF animal models as therapeutic read-outs in vivo are more complex. Contributing to the development of both novel pharmacological as well as genetic treatment strategies will hopefully increase the chance of developing a cure for the majority of CF patients in the near future.

Keywords:Mucoviscidose, Gentherapie, Lentivirale en adeno-geassocieerde viral, Intestinale organoïden, Nasale potentiaal metingen, Muco muismodel

Disciplines:Microbiology, Systems biology, Laboratory medicine