Peter van Mourik

27 R117H function and VX-770 response in organoids with 5T, 9T) and CFTR modulator treatments. Since transcript availability determines the quantity of CFTR that can be restored, variability in mRNA expression might contribute to the heterogeneity in phenotype and treatment responses observed with other CFTR genotypes. This could also indicate that interventions that increase CFTR gene expression may have therapeutic benefit. Linking CFTR mRNA expression to clinical disease severity and variability in drug response is needed to determine the clinical implications of our findings. This study would suggest that differences in mRNA expression may be useful as an additional diagnostic tool for both disease prognosis and (individual) response to CFTR modulator treatment(s). 2