Theratyping for personalized medicine across cystic fibrosis disease models

In the era of CFTR modulators, cystic fibrosis (CF) is being profoundly reshaped for treatment-eligible individuals. Theratyping, an ex vivo strategy assessing individual responses to CFTR modulators, supports precision medicine, particularly for rare variants where conventional trials are limited. In this Review, we discussed advances in CF disease modelling, highlighting strengths, limitations and translational relevance. We also outlined future directions aligned with the Replacement, Reduction, and Refinement (3 R) ethical principles in animal research, including organ-on-a-chip technologies, to improve mechanistic insight and preclinical predictivity. CF research offers therefore a paradigmatic framework for therapeutic innovation in other rare genetic diseases.