Table 1: Preclinical model systems for theratyping.

Model system	Source	Level of advancement	Most common uses
Transient CFTR expression in heterologous cell lines	Established cell lines	high	Characterize CFTR variants and CFTR biology
Stable CFTR transduction in cell lines	Established cell lines	high	HTS screening, evaluate common and rare CFTR variants in standardized system
Human bronchial airway epithelial (HBE) planar cultures	Lung explant	high	Validation of CFTR modulation in primary human cells, assess downstream effects (e.g. mucocilary clearance, airway surface liquid height)
Rectal organoids	Rectal biopsy	moderate	Validation of CFTR modulation in primary human cells, and patient-specific responses to modulators (fluid secretion)
Duodenal enteroids	Duodenal biopsy	low	Similar to rectal organoids Above
HBE planar cultures from brush	Bronchial brush	low	Similar to HBEs from lung explant, and patient-specific responses to modulators (ion transport)
Human nasal epithelial (HNE) planar cultures from brush	Nasal brush	low	Similar to HBEs from lung explant, and patient-specific responses to modulators (ion transport)
HNE spheres	Nasal brush	low	Similar to HBEs from lung explant, and patient-specific responses to modulators (fluid transport)
Induced pluripotent stem cells (iPSCs)	Blood	low	Differentiation into CFTR- expressing epithelial cells and tissues