Peter van Mourik

175 Rationale of the HIT-CF Organoid study REFERENCES 1. Kerem, B. et al. Identification of the cystic fibrosis gene: genetic analysis. Science 245 , 1073–80 (1989). 2. De Boeck, K. & Amaral, M. D. Progress in therapies for cystic fibrosis. Lancet Respir. Med. 2600 , 1–13 (2016). 3. Elborn, J. S. Cystic fibrosis. Lancet (2016) doi:10.1016/S0140-6736(16)00576-6. 4. Cystic Fibrosis Mutation Database. http://www.genet.sickkids.on.ca/. 5. The Clinical and Functional TRanslation of CFTR (CFTR2); available at http:// cftr2.org. 6. Kerem, E. et al. The Relation between genotype and phenotype in Cystic Fibrosis - Analysis of the most common mutation (F508del). N. Engl. J. Med. 323 , 1517–22 (1990). 7. Van Goor, F. et al. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc. Natl. Acad. Sci. 106 , 18825–18830 (2009). 8. Boyle, M. P. et al. A CFTR corrector (lumacaftor) and a CFTR potentiator (ivacaftor) for treatment of patients with cystic fibrosis who have a phe508del CFTR mutation: A phase 2 randomised controlled trial. Lancet Respir. Med. 2 , 527–538 (2014). 9. Wainwright, C. E. et al. Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR. N. Engl. J. Med. 1–12 (2015) doi:10.1056/ NEJMoa1409547. 10. Van Goor, F. et al. Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc. Natl. Acad. Sci. 108 , 18843– 18848 (2011). 11. Cuyx, S. & De Boeck, K. Treating the Underlying Cystic Fibrosis Transmembrane Conductance Regulator Defect in Patients with Cystic Fibrosis. Semin. Respir. Crit. Care Med. (2019) doi:10.1055/s-0039-1696664. 12. Veit, G. et al. Structure-guided combination therapy to potently improve the function of mutant CFTRs. Nat. Med. 24 , 1732–1742 (2018). 13. Veit, G. et al. Mutation-specific dual potentiators maximize rescue of CFTR gating mutants. J. Cyst. Fibros. (2019) doi:10.1016/j.jcf.2019.10.011. 14. Heijerman, H. G. M. et al. Efficacy and safety of the elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet (London, England) 6736 , 6–14 (2019). 15. Middleton, P. G. et al. Elexacaftor–Tezacaftor–Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N. Engl. J. Med. 381 , 1809–1819 (2019). 16. Welch, E. M. et al. PTC124 targets genetic disorders caused by nonsense mutations. Nature 447 , 87–91 (2007). 17. Dukovski, D. et al. Amplifiers co-translationally enhance CFTR biosynthesis via PCBP1-mediated regulation of CFTR mRNA. J. Cyst. Fibros. 1–9 (2020) doi:10.1016/j.jcf.2020.02.006. 8