This study is the extension of the FFC#12/2018 project, and it will be dedicated to studying the efficacy of CFTR modulators in nasal epithelial cells through ex vivo tests, which will also include organoids grown from stem cells. The aim is, above all, to study the epithelia of CF patients carrying rare mutations – specifically 31 genotypes will be evaluated -– which are not among those treatable with currently approved CFTR modulators; the goal is therefore to develop personalized therapies to target the basic defect in CF (i.e. theratyping ). The samples will be tested and a comparison will be performed in relation to the effects of the currently approved modulators Orkambi, Symkevi and Kaftrio. Moreover, a new therapeutic protocol, aimed at increasing the CFTR expression and transportation of chloride ions through specific cell’s ion-transporters (called “ionocytes”), will be evaluated.