Challenges in CF
CF is a genetic disease that is caused by mutations of the gene encoding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Mutations in CFTR gen lead to impaired protein function causing severe damage to the lungs, digestive system and other organs in the body. A major problem in treating CF is the diversity of the genetic defect. More than 2000 different mutations have been identified in CF patients, with only 12 common mutations being represented in 50% of the CF population and more than 1900 rare mutations being distributed in the other 50%. For CF patients with common mutations, effective medication is available. However, for the group with rare mutations, there is no treatment available emphasizing the importance and the value of patient-derived organoids in drug development and diagnostic.
CRISPR-based adenine editors correct nonsense mutations in a cystic fibrosis organoid biobank. M.H. Geurts*, E. de Poel*, G.D. Amatngalim, R. Oka, F.M. Meijers, E. Kruisselbrink, P. van Mourik, G. Berkers, K.M. de Winter-de Groot, S. Michel, D. Muilwijk, B.L. Aalbers, J. Mullenders, S.F. Boj, S.W.F. Suen3, J.E. Brunsveld, H.M. Janssens, M.A. Mall, S.Y. Graeber, R. van Boxtel, C.K. van der Ent, J.M. Beekman†, H. Clevers†. Cell Stem Cell 2020.