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Review

Precision Medicine Based on CFTR Genotype for People with Cystic Fibrosis

, ORCID Icon, , & ORCID Icon
Pages 91-104 | Published online: 05 Feb 2022

References

  • Riordan J, Rommens J, Kerem B, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989;245(4922):1066–1073. doi:10.1126/science.2475911
  • Shteinberg M, Haq IJ, Polineni D, Davies JC. Cystic fibrosis. Lancet. 2021;397(10290):2195–2211. doi:10.1016/S0140-6736(20)32542-3
  • Castellani C, Massie J, Sontag M, Southern KW. Newborn screening for cystic fibrosis. Lancet Respir Med. 2016;4(8):653–661. doi:10.1016/S2213-2600(16)00053-9
  • Trust C. UK cystic fibrosis registry annual data report 2019; 2020. Available from: https://www.cysticfibrosis.org.uk/sites/default/files/2020-12/2019%20Registry%20Annual%20Data%20report_Sep%202020.pdf. Accessed January 26, 2022.
  • Cystic Fibrosis Trust. Cystic Fibrosis Trust: Standards for the Clinical Care of Children and Adults with Cystic Fibrosis in the UK. Second ed. Cystic Fibrosis Trust; 2021.
  • Zielenski J, Rozmahel R, Bozon D, et al. Genomic DNA sequence of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Genomics. 1991;10(1):214–228. doi:10.1016/0888-7543(91)90503-7
  • Sheppard DN, Welsh MJ. Structure and function of the CFTR chloride channel. Physiol Rev. 1999;79(1):S23–S45. doi:10.1152/physrev.1999.79.1.S23
  • Hwang T-C, Sheppard DN. Gating of the CFTR Cl− channel by ATP-driven nucleotide-binding domain dimerisation. J Physiol. 2009;587(10):2151–2161. doi:10.1113/jphysiol.2009.171595
  • Vergani P, Lockless SW, Nairn AC, Gadsby DC. CFTR channel opening by ATP-driven tight dimerization of its nucleotide-binding domains. Nature. 2005;433:876. doi:10.1038/nature03313
  • Schloesser M, Arleth S, Lenz U, Bertele RM, Reiss J. A cystic fibrosis patient with the nonsense mutation G542X and the splice site mutation 1717-1. J Med Genet. 1991;28(12):878. doi:10.1136/jmg.28.12.878
  • Sheppard DN, Rich DP, Ostedgaard LS, Gregory RJ, Smith AE, Welsh MJ. Mutations in CFTR associated with mild-disease-form CI- channels with altered pore properties. Nature. 1993;362(6416):160–164. doi:10.1038/362160a0
  • Beck S, Penque D, Garcia S, et al. Cystic fibrosis patients with the 3272-26A→G mutation have mild disease, leaky alternative mRNA splicing, and CFTR protein at the cell membrane. Hum Mutat. 1999;14(2):133–144. doi:10.1002/(SICI)1098-1004(1999)14:2<133::AID-HUMU5>3.0.CO;2-T
  • Ramalho AS, Lewandowska MA, Farinha CM, et al. Deletion of CFTR translation start site reveals functional isoforms of the protein in CF patients. Cell Physiol Biochem. 2009;24(5–6):335–346. doi:10.1159/000257426
  • Mishra A, Greaves R, Smith K, et al. Diagnosis of cystic fibrosis by sweat testing: age-specific reference intervals. J Pediatr. 2008;153(6):758–763.e1. doi:10.1016/j.jpeds.2008.04.067
  • Haq IJ, Gray MA, Garnett JP, Ward C, Brodlie M. Airway surface liquid homeostasis in cystic fibrosis: pathophysiology and therapeutic targets. Thorax. 2016;71(3):284–287. doi:10.1136/thoraxjnl-2015-207588
  • Morrison CB, Markovetz MR, Ehre C. Mucus, mucins, and cystic fibrosis. Pediatr Pulmonol. 2019;54(Suppl 3):S84–S96. doi:10.1002/ppul.24530
  • Pezzulo AA, Tang XX, Hoegger MJ, et al. Reduced airway surface pH impairs bacterial killing in the porcine cystic fibrosis lung. Nature. 2012;487(7405):109–113. doi:10.1038/nature11130
  • Keown K, Brown R, Doherty DF, et al. Airway inflammation and host responses in the era of CFTR modulators. Int J Mol Sci. 2020;21(17):6379. doi:10.3390/ijms21176379
  • Coutinho HDM, Falcão-Silva VS, Gonçalves GF. Pulmonary bacterial pathogens in cystic fibrosis patients and antibiotic therapy: a tool for the health workers. Int Arch Med. 2008;1(1):24. doi:10.1186/1755-7682-1-24
  • Jones AP, Wallis C. Dornase alfa for cystic fibrosis. Cochrane Database Syst Rev. 2010;(3). doi:10.1002/14651858.CD001127.pub2
  • Fuchs HJ, Borowitz DS, Christiansen DH, et al. Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. N Engl J Med. 1994;331(10):637–642. doi:10.1056/NEJM199409083311003
  • Elkins MR, Robinson M, Rose BR, et al. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med. 2006;354(3):229–240. doi:10.1056/NEJMoa043900
  • Main E, Prasad A, van der Schans CP. Conventional chest physiotherapy compared to other airway clearance techniques for cystic fibrosis. Cochrane Database Syst Rev. 2005;(1). doi:10.1002/14651858.CD002011.pub2
  • Somaraju URR, Solis-Moya A. Pancreatic enzyme replacement therapy for people with cystic fibrosis. Cochrane Database Syst Rev. 2020;(8). doi:10.1002/14651858.CD008227.pub4
  • Stern RC, Eisenberg JD, Wagener JS, et al. A comparison of the efficacy and tolerance of pancrelipase and placebo in the treatment of steatorrhea in cystic fibrosis patients with clinical exocrine pancreatic insufficiency. Am J Gastroenterol. 2000;95(8):1932–1938. doi:10.1016/S0002-9270(00)01036-4
  • Nutritional basics. Available from: https://www.cff.org/Life-With-CF/Daily-Life/Fitness-and-Nutrition/Nutrition/Getting-Your-Nutrients/Nutritional-Basics/. Accessed February 22, 2021.
  • Hollander FM, de Roos NM, Dopheide J, Hoekstra T, van Berkhout FT. Self-reported use of vitamins and other nutritional supplements in adult patients with cystic fibrosis. Is daily practice in concordance with recommendations? Int J Vitamin Nutr Res. 2010;80(6):408–415. doi:10.1024/0300-9831/a000025
  • Boëlle P-Y, Debray D, Guillot L, Clement A, Corvol H; on behalf of the French CFMGSI. Cystic fibrosis liver disease: outcomes and risk factors in a large cohort of French patients. Hepatology. 2019;69(4):1648–1656. doi:10.1002/hep.30148
  • Moran A, Dunitz J, Nathan B, Saeed A, Holme B, Thomas W. Cystic fibrosis–related diabetes: current trends in prevalence, incidence, and mortality. Diabetes Care. 2009;32(9):1626. doi:10.2337/dc09-0586
  • Marshall BC, Butler SM, Stoddard M, Moran AM, Liou TG, Morgan WJ. Epidemiology of cystic fibrosis-related diabetes. J Pediatr. 2005;146(5):681–687. doi:10.1016/j.jpeds.2004.12.039
  • Chillón M, Casals T, Mercier B, et al. Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. N Engl J Med. 1995;332(22):1475–1480. doi:10.1056/NEJM199506013322204
  • Van Goor F, Hadida S, Grootenhuis PDJ, et al. Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Am Thorac Soc. 2009;106(44):18825–18830. doi:10.1073/pnas.0904709106
  • Eckford PD, Li C, Ramjeesingh M, Bear CE. Cystic fibrosis transmembrane conductance regulator (CFTR) potentiator VX-770 (ivacaftor) opens the defective channel gate of mutant CFTR in a phosphorylation-dependent but ATP-independent manner. J Biol Chem. 2012;287(44):36639–36649. doi:10.1074/jbc.M112.393637
  • Liu F, Zhang Z, Levit A, et al. Structural identification of a hotspot on CFTR for potentiation. Science. 2019;364(6446):1184–1188. doi:10.1126/science.aaw7611
  • Ramsey BW, Davies J, McElvaney NG, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011;365(18):1663–1672. doi:10.1056/NEJMoa1105185
  • Davies JC, Wainwright CE, Canny GJ, et al. Efficacy and safety of ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation. Am J Respir Crit Care Med. 2013;187(11):1219–1225. doi:10.1164/rccm.201201-0153OC
  • De Boeck K, Munck A, Walker S, et al. Efficacy and safety of ivacaftor in patients with cystic fibrosis and a non-G551D gating mutation. J Cyst Fibros. 2014;13(6):674–680. doi:10.1016/j.jcf.2014.09.005
  • Rosenfeld M, Cunningham S, Harris WT, et al. An open-label extension study of ivacaftor in children with CF and a CFTR gating mutation initiating treatment at age 2–5 years (KLIMB). J Cystic Fibrosis. 2019;18(6):838–843. doi:10.1016/j.jcf.2019.03.009
  • Davies JC, Cunningham S, Harris WT, et al. Safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2–5 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study. Lancet Respir Med. 2016;4(2):107–115. doi:10.1016/S2213-2600(15)00545-7
  • Moss RB, Flume PA, Elborn JS, et al. Efficacy and safety of ivacaftor in patients with cystic fibrosis who have an Arg117His-CFTR mutation: a double-blind, randomised controlled trial. Lancet Respir Med. 2015;3(7):524–533. doi:10.1016/S2213-2600(15)00201-5
  • Davies JC, Wainwright CE, Sawicki GS, et al. Ivacaftor in infants aged 4 to <12 months with cystic fibrosis and a gating mutation. results of a two-part phase 3 clinical trial. Am J Respir Crit Care Med. 2021;203(5):585–593. doi:10.1164/rccm.202008-3177OC
  • England NHS. Clinical Commissioning Urgent Policy Statement Ivacaftor and tezacaftor/ivacaftor for cystic fibrosis: “off-label” use in patients with named rarer mutations; 2021. Available from: https://www.england.nhs.uk/wp-content/uploads/2020/08/Urgent-policy-statement-CFTR-off-label-rarer-mutations.pdf. Accessed January 26, 2022.
  • Van Goor F, Hadida S, Grootenhuis PD, et al. Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc Natl Acad Sci U S A. 2011;108(46):18843–18848. doi:10.1073/pnas.1105787108
  • Clancy J, Rowe SM, Accurso FJ, et al. Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the F508del-CFTR mutation. Thorax. 2012;67(1):12–18. doi:10.1136/thoraxjnl-2011-200393
  • Boyle MP, Bell SC, Konstan MW, 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. 2014;2(7):527–538. doi:10.1016/S2213-2600(14)70132-8
  • Wainwright CE, Elborn JS, Ramsey BW, et al. Lumacaftor–ivacaftor in patients with cystic fibrosis homozygous for Phe508del CFTR. N Engl J Med. 2015;373(3):220–231. doi:10.1056/NEJMoa1409547
  • Ratjen F, Hug C, Marigowda G, et al. Efficacy and safety of lumacaftor and ivacaftor in patients aged 6–11 years with cystic fibrosis homozygous for F508del-CFTR: a randomised, placebo-controlled phase 3 trial. Lancet Respir Med. 2017;5(7):557–567. doi:10.1016/S2213-2600(17)30215-1
  • McNamara JJ, McColley SA, Marigowda G, et al. Safety, pharmacokinetics, and pharmacodynamics of lumacaftor and ivacaftor combination therapy in children aged 2–5 years with cystic fibrosis homozygous for F508del-CFTR: an open-label phase 3 study. Lancet Respir Med. 2019;7(4):325–335. doi:10.1016/S2213-2600(18)30460-0
  • Taylor-Cousar JL, Munck A, McKone EF, et al. Tezacaftor–ivacaftor in patients with cystic fibrosis homozygous for Phe508del. N Engl J Med. 2017;377(21):2013–2023. doi:10.1056/NEJMoa1709846
  • Schwarz C, Sutharsan S, Epaud R, et al. Tezacaftor/ivacaftor in people with cystic fibrosis who stopped lumacaftor/ivacaftor due to respiratory adverse events. J Cyst Fibros. 2021;20(2):228–233. doi:10.1016/j.jcf.2020.06.001
  • Rowe SM, Daines C, Ringshausen FC, et al. Tezacaftor–ivacaftor in residual-function heterozygotes with cystic fibrosis. N Engl J Med. 2017;377(21):2024–2035. doi:10.1056/NEJMoa1709847
  • Munck A, Kerem E, Ellemunter H, et al. Tezacaftor/ivacaftor in people with cystic fibrosis heterozygous for minimal function CFTR mutations. J Cyst Fibros. 2020;19(6):962–968. doi:10.1016/j.jcf.2020.04.015
  • McKone EF, DiMango EA, Sutharsan S, et al. A phase 3, randomized, double-blind, parallel-group study to evaluate tezacaftor/ivacaftor in people with cystic fibrosis heterozygous for F508del-CFTR and a gating mutation. J Cyst Fibros. 2021;20(2):234–242. doi:10.1016/j.jcf.2020.11.003
  • Okiyoneda T, Veit G, Dekkers JF, et al. Mechanism-based corrector combination restores DeltaF508-CFTR folding and function. Nat Chem Biol. 2013;9(7):444–454. doi:10.1038/nchembio.1253
  • Davies JC, Moskowitz SM, Brown C, et al. VX-659–tezacaftor–ivacaftor in patients with cystic fibrosis and one or two Phe508del alleles. N Engl J Med. 2018;379(17):1599–1611. doi:10.1056/NEJMoa1807119
  • Keating D, Marigowda G, Burr L, et al. VX-445–tezacaftor–ivacaftor in patients with cystic fibrosis and one or two Phe508del alleles. N Engl J Med. 2018;379(17):1612–1620. doi:10.1056/NEJMoa1807120
  • Middleton PG, Mall MA, Dřevínek P, et al. Elexacaftor–tezacaftor–ivacaftor for cystic fibrosis with a single Phe508del allele. N Engl J Med. 2019;381(19):1809–1819. doi:10.1056/NEJMoa1908639
  • Heijerman HGM, McKone EF, Downey DG, 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. 2019;394(10212):1940–1948. doi:10.1016/S0140-6736(19)32597-8
  • Clinicaltrials.gov. A phase 3 study of VX-659 combination therapy in subjects with cystic fibrosis heterozygous for the F508del mutation and a minimal function mutation (F/MF); 2021. Available from: https://clinicaltrials.gov/ct2/show/results/NCT03447249. Accessed January 26, 2022.
  • Vertex. Two phase 3 studies of the triple combination of VX-659, tezacaftor and ivacaftor met primary endpoint of improvement in lung function (ppFEV1) in people with cystic fibrosis; 2022. Available from: https://investors.vrtx.com/news-releases/news-release-details/two-phase-3-studies-triple-combination-vx-659-tezacaftor-and. Accessed January 14, 2022.
  • Vertex. Vertex selects triple combination regimen of VX-445, tezacaftor and ivacaftor to submit for global regulatory approvals in cystic fibrosis; 2022. Available from: https://investors.vrtx.com/news-releases/news-release-details/vertex-selects-triple-combination-regimen-vx-445-tezacaftor-and. Accessed January 14, 2022.
  • England NHS. ‘Miracle’ cystic fibrosis treatment for children on the NHS; 2022. Available from: https://www.england.nhs.uk/2022/01/miracle-cystic-fibrosis-treatment-for-children-on-the-nhs/. Accessed January 14, 2022.
  • Barry PJ, Mall MA, Álvarez A, et al. Triple therapy for cystic fibrosis Phe508del–gating and –residual function genotypes. N Engl J Med. 2021;385(9):815–825. doi:10.1056/NEJMoa2100665
  • Duckers J, Lesher B, Thorat T, et al. Real-world outcomes of ivacaftor treatment in people with cystic fibrosis: a systematic review. J Clin Med. 2021;10(7):1527. doi:10.3390/jcm10071527
  • Mitchell RM, Jones AM, Stocking K, Foden P, Barry PJ. Longitudinal effects of ivacaftor and medicine possession ratio in people with the Gly551Asp mutation: a 5-year study. Thorax. 2021;76(9):874–879. doi:10.1136/thoraxjnl-2020-215556
  • Guimbellot JS, Baines A, Paynter A, et al. Long term clinical effectiveness of ivacaftor in people with the G551D CFTR mutation. J Cyst Fibros. 2021;20(2):213–219. doi:10.1016/j.jcf.2020.11.008
  • Emery J, Mullane D, Chroinin MN. GP284 The effects of ivacaftor on pancreatic function in paediatric patients with cystic fibrosis gating mutations. Arch Dis Child. 2019;104(Suppl 3):A149–A150. doi:10.1136/archdischild-2019-epa.343
  • Barry PJP, Simmonds BJ, Bicknell NJ, et al. Ivacaftor decreases mortality in G551D patients with severe lung disease. Pediatr Pulmonol. 2015;50:275–276.
  • Burgel PR, Munck A, Durieu I, et al. Real-life safety and effectiveness of lumacaftor-ivacaftor in patients with cystic fibrosis. Am J Respir Crit Care Med. 2020;201(2):188–197. doi:10.1164/rccm.201906-1227OC
  • Benden C, Schwarz C. CFTR modulator therapy and its impact on lung transplantation in cystic fibrosis. Pulm Ther. 2021;7(2):377–393. doi:10.1007/s41030-021-00170-9
  • O’Shea KM, O’Carroll OM, Carroll C, et al. Efficacy of elexacaftor/tezacaftor/ivacaftor in patients with cystic fibrosis and advanced lung disease. Eur Respir J. 2021;57(2). doi:10.1183/13993003.03079-2020
  • Dagenais RVE, Su VCH, Quon BS. Real-world safety of CFTR modulators in the treatment of cystic fibrosis: a systematic review. J Clin Med. 2020;10(1):23. doi:10.3390/jcm10010023
  • Heo S, Young DC, Safirstein J, et al. Mental status changes during elexacaftor/tezacaftor/ivacaftor therapy. J Cyst Fibros. 2021. doi:10.1016/j.jcf.2021.10.002
  • Zainal Abidin N, Haq IJ, Gardner AI, Brodlie M. Ataluren in cystic fibrosis: development, clinical studies and where are we now? Expert Opin Pharmacother. 2017;18(13):1363–1371. doi:10.1080/14656566.2017.1359255
  • Kerem E, Konstan MW, De Boeck K, et al. A randomized placebo-controlled trial of ataluren for the treatment of nonsense mutation cystic fibrosis. Lancet Respir Med. 2014;2(7):539–547. doi:10.1016/S2213-2600(14)70100-6
  • Konstan MW, VanDevanter DR, Rowe SM, et al. Efficacy and safety of ataluren in patients with nonsense-mutation cystic fibrosis not receiving chronic inhaled aminoglycosides: the international, randomized, double-blind, placebo-controlled Ataluren Confirmatory Trial in Cystic Fibrosis (ACT CF). J Cystic Fibrosis. 2020;19:1873–5010.
  • Dukovski D, Villella A, Bastos C, et al. Amplifiers co-translationally enhance CFTR biosynthesis via PCBP1-mediated regulation of CFTR mRNA. J Cyst Fibros. 2020;19(5):733–741. doi:10.1016/j.jcf.2020.02.006
  • Giuliano KA, Wachi S, Drew L, et al. Use of a high-throughput phenotypic screening strategy to identify amplifiers, a novel pharmacological class of small molecules that exhibit functional synergy with potentiators and correctors. SLAS Discov. 2018;23(2):111–121. doi:10.1177/2472555217729790
  • Cystic Fibrosis Foundation. Drug development pipeline; 2021. Available from: https://apps.cff.org/trials/pipeline/details/10145/ABBV-2222-formerly-GLPG2222. Accessed January 26, 2022.
  • Bell SC, Barry PJ, De Boeck K, et al. CFTR activity is enhanced by the novel corrector GLPG2222, given with and without ivacaftor in two randomized trials. J Cyst Fibros. 2019;18(5):700–707. doi:10.1016/j.jcf.2019.04.014
  • Clinicaltrials.gov. Study to evaluate adverse events and change in disease activity with oral capsules of galicaftor/navocaftor/ABBV-119 combination therapy in adult participants with cystic fibrosis; 2021. Available from: https://clinicaltrials.gov/ct2/show/NCT04853368. Accessed January 26, 2022.
  • Egan ME. Emerging technologies for cystic fibrosis transmembrane conductance regulator restoration in all people with CF. Pediatr Pulmonol. 2021;56(Suppl 1):S32–S39. doi:10.1002/ppul.24965
  • Goemans N. Gene therapy for spinal muscular atrophy: hope and caution. Lancet Neurol. 2021;20(4):251–252. doi:10.1016/S1474-4422(21)00071-5
  • Alton E, Armstrong DK, Ashby D, et al. Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial. Lancet Respir Med. 2015;3(9):684–691. doi:10.1016/S2213-2600(15)00245-3
  • Christopher Boyd A, Guo S, Huang L, et al. New approaches to genetic therapies for cystic fibrosis. J Cyst Fibros. 2020;19(Suppl 1):S54–S59. doi:10.1016/j.jcf.2019.12.012
  • Ensinck M, Mottais A, Detry C, Leal T, Carlon MS. On the corner of models and cure: gene editing in cystic fibrosis. Front Pharmacol. 2021;12:662110. doi:10.3389/fphar.2021.662110
  • Brodlie M, Haq IJ, Roberts K, Elborn JS. Targeted therapies to improve CFTR function in cystic fibrosis. Genome Med. 2015;7:101. doi:10.1186/s13073-015-0223-6
  • Montoro DT, Haber AL, Biton M, et al. A revised airway epithelial hierarchy includes CFTR-expressing ionocytes. Nature. 2018;560(7718):319–324. doi:10.1038/s41586-018-0393-7
  • Bessonova L, Volkova N, Higgins M, et al. Data from the US and UK cystic fibrosis registries support disease modification by CFTR modulation with ivacaftor. Thorax. 2018;73(8):731–740. doi:10.1136/thoraxjnl-2017-210394
  • Volkova N, Moy K, Evans J, et al. Disease progression in patients with cystic fibrosis treated with ivacaftor: data from national US and UK registries. J Cyst Fibros. 2020;19(1):68–79. doi:10.1016/j.jcf.2019.05.015
  • Mayer-Hamblett N, Nichols DP, Odem-Davis K, et al. Evaluating the impact of stopping chronic therapies after modulator drug therapy in cystic fibrosis: the SIMPLIFY clinical trial study design. Ann Am Thorac Soc. 2021;18(8):1397–1405. doi:10.1513/AnnalsATS.202010-1336SD
  • Amaral MD, de Boeck K, Amaral M, et al. Theranostics by testing CFTR modulators in patient-derived materials: the current status and a proposal for subjects with rare CFTR mutations. J Cyst Fibros. 2019;18(5):685–692. doi:10.1016/j.jcf.2019.06.010
  • Haq IJ, Althaus M, Gardner AI, et al. Clinical and molecular characterization of the R751L-CFTR mutation. Am J Physiol Lung Cell Mol Physiol. 2021;320(2):L288–L300. doi:10.1152/ajplung.00137.2020
  • Dekkers JF, Berkers G, Kruisselbrink E, et al. Characterizing responses to CFTR-modulating drugs using rectal organoids derived from subjects with cystic fibrosis. Sci Transl Med. 2016;8:344ra84–344ra84. doi:10.1126/scitranslmed.aad8278
  • Sette G, Lo Cicero S, Blaconà G, et al. Theratyping cystic fibrosis in vitro in ALI culture and organoid models generated from patient-derived nasal epithelial conditionally reprogrammed stem cells. Eur Respir J. 2021;58:2100908. doi:10.1183/13993003.00908-2021
  • Merkert S, Bednarski C, Göhring G, Cathomen T, Martin U. Generation of a gene-corrected isogenic control iPSC line from cystic fibrosis patient-specific iPSCs homozygous for p.Phe508del mutation mediated by TALENs and ssODN. Stem Cell Res. 2017;23:95–97. doi:10.1016/j.scr.2017.07.010
  • Matthes E, Goepp J, Martini C, et al. Variable responses to CFTR correctors in vitro: estimating the design effect in precision medicine. Front Pharmacol. 2018;9(1490). doi:10.3389/fphar.2018.01490
  • Lopes-Pacheco M. CFTR modulators: the changing face of cystic fibrosis in the era of precision medicine. Front Pharmacol. 2019;10:1662. doi:10.3389/fphar.2019.01662
  • Pinto MC, Silva IAL, Figueira MF, Amaral MD, Lopes-Pacheco M. Pharmacological modulation of ion channels for the treatment of cystic fibrosis. J Exp Pharmacol. 2021;13:693–723. doi:10.2147/JEP.S255377
  • Liu F, Zhang Z, Csanady L, Gadsby DC, Chen J. Molecular structure of the human CFTR ion channel. Cell. 2017;169(1):85–95 e8. doi:10.1016/j.cell.2017.02.024
  • Zhang Z, Liu F, Chen J. Molecular structure of the ATP-bound, phosphorylated human CFTR. Proc Natl Acad Sci U S A. 2018;115(50):12757–12762. doi:10.1073/pnas.1815287115