Evaluation of CFTR Channel Functions and Responses to Modulators in Patients with Cystic Fibrosis who Have a Pathogenic F508del Variant in Their Genomes

Intestinal organoids derived from rectal biopsies of cystic fibrosis patients are a highly sensitive personalized method for evaluating the functional activity of the CFTR channel and the efficacy of target drugs. We examined four patients whose genotype contains the pathogenic F508del variant (three patients and one healthy heterozygous person). It was shown that F508del/F508del genotype (two patients) could be effectively corrected by CFTR modulators (VX-770 and VX-809). The modulators had no significant effect on the restoration of the chlorine CFTR channel function in a patient with the W361X/F508del genotype. The CFTR functional activity in the heterozygous F508del carrier was as high as in the healthy control. cystic fibrosis, intestinal organoids, genetic F508del variant, genotype, forskolin-induced swelling (FIS) assay, CFTR modulators This study was supported by the Ministry of Science and Higher Education as part of a State Assignment for RCMG.