Progress Towards Next-Generation Therapeutics for Cystic Fibrosis

References

• Muller F , AubryMC, GasserB, DuchatelF, BouéJ, BouéA. Prenatal diagnosis of cystic fibrosis. II. Meconium ileus in affected fetuses. Prenatal Diagn.5 (2), 109–117 (1985).
   PubMed Web of Science ®Google Scholar
• Farrelly PJ , CharlesworthC, LeeS, SouthernKW, BaillieCT. Gastrointestinal surgery in cystic fibrosis: a 20-year review. J. Pediatr. Surg.49 (2), 280–283 (2014).
   PubMed Web of Science ®Google Scholar
• Nash KL , AllisonME, McKeonD, LomasDJ, HaworthCS, BiltonD, AlexanderGJ. A single centre experience of liver disease in adults with cystic fibrosis 1995–2006. J. Cyst. Fibros.7 (3), 252–257 (2007).
   PubMed Web of Science ®Google Scholar
• Cheng K , AshbyD, SmythRL. Ursodeoxycholic acid for cystic fibrosis-related liver disease. Cochrane Database Syst. Rev.10, CD000222 (2012).
   PubMedGoogle Scholar
• Aanæs K . Bacterial sinusitis can be a focus for initial lung colonisation and chronic lung infection in patients with cystic fibrosis. J. Cyst. Firbros.12 (Suppl. 2), S1–S20 (2013).
   PubMed Web of Science ®Google Scholar
• Cox MJ , AllgaierM, TaylorBet al. Airway microbiota and pathogen abundance in age-stratified cystic fibrosis patients. PLoS ONE5 (6), e11044 (2010).
   PubMed Web of Science ®Google Scholar
• Wolter DJ , EmersonJC, McNamaraSet al. Staphylococcus aureus small-colony variants are independently associated with worse lung disease in children with cystic fibrosis. Clin. Infect. Dis.57 (3), 384–391 (2013).
   PubMed Web of Science ®Google Scholar
• Quinn RA , LimYW, MaughanH, ConradD, RohwerF, WhitesonKL. Biogeochemical forces shape the composition and physiology of polymicrobial communities in the cystic fibrosis lung. MBio5 (2), e00956–e01013 (2014).
   PubMed Web of Science ®Google Scholar
• Zach MS , OberwaldnerB. Chest physiotherapy – the mechanical approach to antiinfective therapy in cystic fibrosis. Infection15 (5), 381–384 (1987).
   PubMed Web of Science ®Google Scholar
• Main E , PrasadA, SchansC. Conventional chest physiotherapy compared with other airway clearance techniques in cystic fibrosis. Cochrane Database Syst. Rev.1, CD002011 (2005).
   Google Scholar
• McKoy NA , SaldanhaIJ, OdelolaOA, RobinsonKA. Active cycle of breathing technique for cystic fibrosis. Cochrane Database Syst. Rev.12, CD007862 (2012).
   PubMedGoogle Scholar
• Letham MI , JamesSL, MarriottC, BurkeJF. The origin of DNA associated with mucus glycoproteins in cystic fibrosis sputum. Eur. Respir. J.3 (1), 19–23 (1990).
   PubMed Web of Science ®Google Scholar
• Rubin B . Mucus, phlegm, and sputum in cystic fibrosis. Respir. Care54 (6), 726–732 (2009).
   PubMed Web of Science ®Google Scholar
• Bragonzi A , WorlitzschD, PierGB, TimpertP, UlrichM, HentzerM, AndersenJB, GivskovM, ConeseM. Nonmucoid Pseudomonas aeruginosa expresses alginate in the lungs of patients with cystic fibrosis and in a mouse model. J. Infect. Dis.192 (3), 410–419 (2005).
   PubMed Web of Science ®Google Scholar
• Fancello L , DesnuesC, RaoultD, RolainJM. Bacteriophages and diffusion of genes encoding antimicrobial resistance in cystic fibrosis sputum microbiota. J. Antimicrob. Chemother.66 (11), 2448–2454 (2011).
   PubMed Web of Science ®Google Scholar
• Ciofu O , MandsbergLF, BjarnsholtT, WassermannT, H⊘ibyN. Genetic adaptation of Pseudomonas aeruginosa during chronic lung infection of patients with cystic fibrosis: strong and weak mutators with heterogeneous genetic backgrounds emerge in mucA and/or lasR mutants. Microbiology156 (Pt 4), 1108–1119 (2010).
   PubMedGoogle Scholar
• Fauvart M1 , De GrooteVN, MichielsJ. Role of persister cells in chronic infections: clinical relevance and perspectives on anti-persister therapies. J. Med. Microbiol.60 (6), 699–709 (2011).
   PubMed Web of Science ®Google Scholar
• Mulcahy LR1 , BurnsJL, LoryS, LewisK. Emergence of Pseudomonas aeruginosa strains producing high levels of persister cells in patients with cystic fibrosis. J. Bacteriol.192 (23), 6191–6199 (2010).
   PubMed Web of Science ®Google Scholar
• Moskwa P , LorentzenD, ExcoffonKJet al. A novel host defense system of airways is defective in cystic fibrosis. Am. J. Respir. Crit. Care Med.175 (2), 174–183 (2007).
   PubMed Web of Science ®Google Scholar
• Zheng S , XuW, BoseS, BanerjeeAK, HaqueSJ, ErzurumSC. Impaired nitric oxide synthase-2 signaling pathway in cystic fibrosis airway epithelium. Am. J. Physiol. Lung Cell. Mol. Physiol.287 (2), L374–L381 (2004).
   PubMed Web of Science ®Google Scholar
• Luciani A , VillellaVR, EspositoSet al. Defective CFTR induces aggresome formation and lung inflammation in cystic fibrosis through ROS-mediated autophagy inhibition. Nat. Cell. Biol.12 (9), 863–875 (2010).
   PubMed Web of Science ®Google Scholar
• Dodge JA , LewisPA, StantonM, WilsherJ. Cystic fibrosis mortality and survival in the UK: 1947–2003. Eur. Resp. J.29, 522–526 (2007).
   PubMed Web of Science ®Google Scholar
• Serisier DJ , TuckA, MatleyD, CarrollMP, JonesG. Antimicrobial susceptibility and synergy studies of cystic fibrosis sputum by direct sputum sensitivity testing. Eur. J. Clin. Microbiol. Infect. Dis.31 (11), 3211–3216.
   PubMed Web of Science ®Google Scholar
• Prayle A , WatsonA, FortnumH, SmythA. Side effects of aminoglycosides on the kidney, ear and balance in cystic fibrosis. Thorax65 (7), 654–658 (2010).
   PubMed Web of Science ®Google Scholar
• De Soyza A , ArcherL, WardleJ, ParryG, DarkJH, GouldK, CorrisPA. Pulmonary transplantation for cystic fibrosis: pre-transplant recipient characteristics in patients dying of peri-operative sepsis. J. Heart Lung Transplant.22 (7), 764–769 (2003).
   PubMed Web of Science ®Google Scholar
• Stutman HR , LiebermanJM, NussbaumE, MarksMI. Antibiotic prophylaxis in infants and young children with cystic fibrosis: a randomized controlled trial. J. Pediatr.140 (3), 299–305 (2002).
   PubMed Web of Science ®Google Scholar
• Ryan G , SinghM, DwanK. Inhaled antibiotics for long-term therapy in cystic fibrosis. Cochrane Database Syst Rev.3, CD001021 (2011).
   PubMed Web of Science ®Google Scholar
• Wagener JS , RasouliyanL, VanDevanterDRet al. Oral, inhaled, and intravenous antibiotic choice for treating pulmonary exacerbations in cystic fibrosis. Pediatr. Pulmonol.48 (7), 666–673 (2013).
   PubMed Web of Science ®Google Scholar
• Cheng K , SmythRL, GovanJRet al. Spread of beta-lactam-resistant Pseudomonas aeruginosa in a cystic fibrosis clinic. Lancet.348 (9028), 639–642 (1996).
   PubMed Web of Science ®Google Scholar
• Scalley RD , ConnerCS. Acetaminophen poisoning: a case report of the use of acetylcysteine. Am. J. Hosp. Pharm.35 (8), 964–967 (1978).
   PubMedGoogle Scholar
• Griese M , KapplerM, EismannCet al. Inhalation treatment with glutathione in patients with cystic fibrosis. A randomized clinical trial. Am. J. Respir. Crit. Care Med.188 (1), 83–89 (2013).
   PubMed Web of Science ®Google Scholar
• Tam J , NashEF, RatjenF, TullisE, StephensonA. Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis. Cochrane Database Syst. Rev.7, CD007168 (2013).
   Google Scholar
• Nasr SZ , ChouW, VillaKF, ChangE, BroderMS. Adherence to dornase alfa treatment among commercially insured patients with cystic fibrosis. J. Med. Econ.16 (6), 801–808 (2013).
   PubMedGoogle Scholar
• Witt DM , AndersonL. Dornase alfa: a new option in the management of cystic fibrosis. Pharmacotherapy16 (1), 40–48 (1996)
   PubMed Web of Science ®Google Scholar
• Wark P , MacDonaldVM. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst. Rev.2, CD001506 (2009).
   Google Scholar
• US FDA. Pulmonary-allergy drugs advisory committee meeting (2013). NDA# 202049: mannitol inhalation powder (proposed trade name Bronchitol®) for oral inhalation sponsored by Pharmaxis, for the management of cystic fibrosis (CF) in patients aged 6 years and older to improve pulmonary function. www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/Pulmonary-AllergyDrugsAdvisoryCommittee/UCM336995.pdf
   Google Scholar
• European Medicines Agency, Committee for Medicinal Products for Human Use (2012). CHMP Assessment Report, Bronchitol®. www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_assessment_report/human/001252/WC500130591.pdf
   Google Scholar
• National Institute for Health and Clinical Excellence (2012). Mannitol dry powder for inhalation for treating cystic fibrosis [online]. www.nice.org.uk/nicemedia/live/13969/61603/61603.pdf
   Google Scholar
• Scottish Medicines Consortium (2013). Mannitol, 400 mg, inhalation powder, hard capsule, (Bronchitol®). www.scottishmedicines.org.uk/files/advice/inhaled_mannitol_Bronchitol_FINAL_January_2013_for_website.pdf
   Google Scholar
• Bilton D , DaviskasE, AndersonSDet al. A Phase III randomised study of the efficacy and safety of inhaled dry powder mannitol (Bronchitol) for the symptomatic treatment of non-cystic fibrosis bronchiectasis. Chest144 (1), 215–225 (2013).
   PubMed Web of Science ®Google Scholar
• Barraud N , BusonA, JarolimekW, RiceSA. Mannitol enhances antibiotic sensitivity of persister bacteria in Pseudomonas aeruginosa biofilms. PLoS ONE8 (12), e84220 (2013).
   PubMed Web of Science ®Google Scholar
• LiPuma JJ . Microbiological and immunologic considerations with aerosolized drug delivery. Chest120, 18S–23S (2001).
   Web of Science ®Google Scholar
• Daniels T , MillsN, WhitakerP. Nebuliser systems for drug delivery in cystic fibrosis. Cochrane Database Syst Rev.4, CD007639 (2013).
   Google Scholar
• Kesser KC , GellerDE. New aerosol delivery devices for cystic fibrosis. Resir. Care.54 (6), 754–767 (2009).
   PubMed Web of Science ®Google Scholar
• Daniels T , GoodacreL, SuttonC, PollardK, ConwayS, PeckhamD. Accurate assessment of adherence: self-report and clinician report vs electronic monitoring of nebulisers. Chest140 (2), 425–432 (2011).
   PubMed Web of Science ®Google Scholar
• Geller DE , WeersJ, HeuerdingS. Development of an inhaled dry-powder formulation of tobramycin using PulmoSphere™ technology. J. Aerosol. Med. Pulm. Drug Deliv.24 (4), 175–182 (2011).
   PubMed Web of Science ®Google Scholar
• Geller DE , NasrSZ, PiggottS, HeE, AngyalosiG, HigginsM. Tobramycin inhalation powder in cystic fibrosis patients: response by age group. Respir. Care doi: 10.4187/respcare.02264 (2013) (Epub ahead of print).
   PubMedGoogle Scholar
• de Vrankrijker AM , van der EntCK, van BerkhoutFTet al. Aspergillus fumigatus colonization in cystic fibrosis: implications for lung function? Clin. Microbiol. Infect. 17 (9), 1381–1386 (2011).
   PubMed Web of Science ®Google Scholar
• Klemmer A , KrämerI, KaminW. Physicochemical compatibility and stability of nebulizable drug admixtures containing dornase alfa and tobramycin. Pulm. Pharmacol. Ther. doi:10.1016/j.pupt.2013.08.003 (2013) (Epub ahead of print).
   PubMed Web of Science ®Google Scholar
• Silvis MR , PiccianoJA, BertrandC, WeixelK, BridgesRJ, BradburyNA. A mutation in the cystic fibrosis transmembrane conductance regulator generates a novel internalization sequence and enhances endocytic rates. J. Biol. Chem.278 (13), 11554–11560 (2003).
   PubMed Web of Science ®Google Scholar
• Welch EM , BartonER, ZhuoJet al. PTC 124 targets genetic disorders caused by nonsense mutations. Nature447 (7140), 87–91 (2007).
   PubMed Web of Science ®Google Scholar
• Rogan MP , StoltzDA, HornickDB. Cystic fibrosis transmembrane conductance regulator intracellular processing, trafficking and opportunities for mutation-specific treatment. Chest139, 1480–1490 (2011).
   PubMed Web of Science ®Google Scholar
• Kerem E , HirawatS, ArmoniSet al. Effectiveness of PTC124 treatment of cystic fibrosis caused by nonsense mutations: a prospective Phase II trial. Lancet372 (9640), 719–727 (2008).
   PubMed Web of Science ®Google Scholar
• Auld, DS, ThorneN, MaguireWF, IngleseJ. Mechanism of PTC124 activity in cell-based luciferase assays of nonsense codon suppression. Proc. Natl Acad. Sci. USA106 (9), 3585–3590 (2009).
   PubMed Web of Science ®Google Scholar
• Auld DS , Lovell S, Thorne Net al. Molecular basis for the high-affinity binding and stabilization of firefly luciferase by PTC124. Proc Natl Acad Sci. USA107 (11), 4878–4883 (2010).
   PubMed Web of Science ®Google Scholar
• McElroy SP , NomuraT, TorrieLSet al. A lack of premature termination codon read-through. PLoS Biol.11 (6), e1001593 (2013).
   PubMed Web of Science ®Google Scholar
• Sermet-Gaudelus I , BoeckKD, CasimirGJet al. Ataluren (PTC124) induces cystic fibrosis transmembrane conductance regulator protein expression and activity in children with nonsense mutation cystic fibrosis. Am. J. Respir. Crit. Care Med.182 (10), 1262–1272 (2010).
   PubMed Web of Science ®Google Scholar
• Cystic Fibrosis Foundation, Clinical research information sheet (2012). Ataluren (PTC 124) in Cystic Fibrosis [online]. www.cff.org/UploadedFiles/ClinicalResearchPDF/CR84.pdf
   Google Scholar
• Drake KM , DunmoreBJ, McNellyLN, MorrellNW, AldredMA. Correction of nonsense BMPR2 and SMAD9 mutations by Ataluren in pulmonary arterial hypertension. Am. J. Respir. Cell. Mol. Biol.49 (3), 403–409 (2013)
   PubMed Web of Science ®Google Scholar
• Li M , Andersson-LendahlM, SejersenT, ArnerA. Muscle dysfunction and structural defects of dystrophin-null sapje mutant zebrafish larvae are rescued by Ataluren treatment. FASEB J.28 (4), 1593–1599 (2013).
   PubMed Web of Science ®Google Scholar
• Finkel RS , FlaniganKM, WongBet al. Phase 2a study of Ataluren-mediated dystrophin production in patients with nonsense mutation duchenne muscular dystrophy. PLoS ONE8 (12), e81302 (2013).
   PubMed Web of Science ®Google Scholar
• Rogan MP , StoltzDA, HornickDB. Cystic fibrosis transmembrane conductance regulator intracellular processing, trafficking and opportunities for mutation-specific treatment. Chest139, 1480–1490 (2011).
   PubMed Web of Science ®Google Scholar
• Van Goor F , HadidaS, GrootenhuisPD Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770 Proc. Natl Acad. Sci. USA. 106 (44), 18825–18830 (2009).
   PubMed Web of Science ®Google Scholar
• Eckford PD , LiC, RamjeesinghM, BearCE. 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.287 (44), 36639–36649 (2012).
   PubMed Web of Science ®Google Scholar
• Jih KY , HwangTC. Vx-770 potentiates CFTR function by promoting decoupling between the gating cycle and ATP hydrolysis cycle. Proc. Natl Acad. Sci. USA110 (11), 4404–4409 (2013).
   PubMed Web of Science ®Google Scholar
• Ramsey BW , DaviesJ, McElvaneyNGet al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N. Engl. J. Med.365 (18), 1663–1672 (2011).
   PubMed Web of Science ®Google Scholar
• Ren HY , GroveDE, De La RosaOet al. VX-809 corrects folding defects in cystic fibrosis transmembrane conductance regulator protein through action on membrane-spanning domain 1. Mol. Biol. Cell.24 (19), 3016–3024 (2013).
   PubMed Web of Science ®Google Scholar
• Loo TW , BartlettMC, ClarkeDM. Corrector VX-809 stabilizes the first transmembrane domain of CFTR. Biochem. Pharmacol.86 (5), 612–619 (2013).
   PubMed Web of Science ®Google Scholar
• Farinha CM , King-UnderwoodJ, SousaMet al. Revertants, low temperature, and correctors reveal the mechanism of F508del-CFTR rescue by VX-809 and suggest multiple agents for full correction. Chem. Biol.20 (7), 943–955 (2013).
   PubMed Web of Science ®Google Scholar
• He L1 , KotaP, AleksandrovAA, CuiL, JensenT, DokholyanNV, RiordanJR. Correctors of ΔF508 CFTR restore global conformational maturation without thermally stabilizing the mutant protein. FASEB J.27 (2), 536–545 (2013).
   PubMed Web of Science ®Google Scholar
• Rabeh WM , BossardF, XuHet al. Correction of both NBD1 energetics and domain interface is required to restore ΔF508 CFTR folding and function. Cell148 (1–2), 150–163 (2012).
   PubMed Web of Science ®Google Scholar
• Okiyoneda T1 , VeitG, DekkersJFet al. Mechanism-based corrector combination restores ΔF508-CFTR folding and function. Nat. Chem. Biol.9 (7), 444–454 (2013).
   PubMed Web of Science ®Google Scholar
• Clancy JP , RoweSM, AccursoFJet 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. Thorax67 (1), 12–18 (2012).
   PubMed Web of Science ®Google Scholar
• Galietta LJ . Managing the underlying cause of cystic fibrosis: a future role for potentiators and correctors. Pediatr. Drugs.15 (5), 393–402 (2013).
   PubMed Web of Science ®Google Scholar
• Farinha CM , King-UnderwoodJ, SousaMet al. Revertants, low temperature, and correctors reveal the mechanism of F508del-CFTR rescue by VX-809 and suggest multiple agents for full correction. Chem. Biol.20 (7), 943–955 (2013).
   PubMed Web of Science ®Google Scholar
• Dowling RB , NewtonR, RobichaudA, ColePJ, BarnesPJ, WilsonR. Effect of inhibition of nitric oxide synthase on Pseudomonas aeruginosa infection of respiratory mucosa in vitro. Am. J. Respir. Cell. Mol. Biol.19 (6), 950–958 (1998).
   PubMed Web of Science ®Google Scholar
• Satoh S , OishiK, IwagakiAet al. Dexamethasone impairs pulmonary defence against Pseudomonas aeruginosa through suppressing iNOS gene expression and peroxynitrite production in mice. Clin. Exp. Immunol.126 (2), 266–273 (2001).
   PubMed Web of Science ®Google Scholar
• Brown RK , KellyFJ. Evidence for increased oxidative damage in patients with cystic fibrosis. Pediatr. Res.36 (4), 487–493 (1994).
   PubMed Web of Science ®Google Scholar
• Brown RK , WyattH, PriceJF, KellyFJ. Pulmonary dysfunction in cystic fibrosis is associated with oxidative stress. Eur. Respir. J.9 (2), 334–339 (1996).
   PubMed Web of Science ®Google Scholar
• Michl RK , HentschelJ, FischerC, BeckJF, MainzJG. Reduced nasal nitric oxide production in cystic fibrosis patients with elevated systemic inflammation markers. PLoS ONE8 (11), e79141 (2013).
   PubMed Web of Science ®Google Scholar
• Walker WT , LiewA, HarrisA, ColeJ, LucasJS. Upper and lower airway nitric oxide levels in primary ciliary dyskinesia, cystic fibrosis and asthma. Respir. Med.107 (3), 380–386 (2013).
   PubMed Web of Science ®Google Scholar
• Grasemann H , SchwiertzR, MatthiesenS, RackéK, RatjenF. Increased arginase activity in cystic fibrosis airways. Am. J. Respir. Crit. Care Med.172 (12), 1523–1528 (2005).
   PubMed Web of Science ®Google Scholar
• Grasemann H , SchwiertzR, GrasemannC, VesterU, RackéK, RatjenF. Decreased systemic bioavailability of L-arginine in patients with cystic fibrosis. Respir. Res.7, 87 (2006).
   PubMed Web of Science ®Google Scholar
• Everard ML , DonnellyD. A pilot study of oral L-arginine in cystic fibrosis. J. Cyst. Fibros.4 (1), 67–69 (2005).
   PubMedGoogle Scholar
• Grasemann H , GrasemannC, KurtzF, Tietze-SchillingsG, VesterU, RatjenF. Oral L-arginine supplementation in cystic fibrosis patients: a placebo-controlled study. Eur. Respir. J.25 (1), 62–68 (2005).
   PubMed Web of Science ®Google Scholar
• Grasemann H , TullisE, RatjenF. A randomized controlled trial of inhaled L-arginine in patients with cystic fibrosis. J. Cyst. Fibros.12 (5), 468–474 (2013).
   PubMed Web of Science ®Google Scholar
• Miller CC , HergottCA, RohanM, Arsenault-MehtaK, DöringG, MehtaS. Inhaled nitric oxide decreases the bacterial load in a rat model of Pseudomonas aeruginosa pneumonia. J. Cyst. Fibros.12 (6), 817–820 (2013).
   PubMed Web of Science ®Google Scholar
• Hopkins N , GunningY, O’CroininDF, LaffeyJG, McLoughlinP. Anti-inflammatory effect of augmented nitric oxide production in chronic lung infection. J. Pathol.209 (2), 198–205 (2006).
   PubMed Web of Science ®Google Scholar
• Chandler JD , MinE, HuangJ, NicholsDP, DayBJ. Nebulized thiocyanate improves lung infection outcomes in mice. Br. J. Pharmacol.169 (5), 1166–1177 (2013).
   PubMed Web of Science ®Google Scholar
• Levine B , KroemerG. Autophagy in aging, disease and death: the true identity of a cell death impostor. Cell Death Differ.16 (1), 1–2 (2009).
   PubMed Web of Science ®Google Scholar
• Junkins RD , ShenA, RosenK, McCormickC, LinTJ. Autophagy enhances bacterial clearance during P. aeruginosa lung infection. PLoS ONE8 (8), e72263 (2013).
   PubMed Web of Science ®Google Scholar
• Rich DP , AndersonMP, GregoryRJet al. Expression of cystic fibrosis transmembrane conductance regulator corrects defective chloride channel regulation in cystic fibrosis airway epithelial cells. Nature347 (6291), 358–363 (1990).
   PubMed Web of Science ®Google Scholar
• Olsen JC , JohnsonLG, StuttsMJ, SarkadiB, YankaskasJR, SwanstromR, BoucherRC. Correction of the apical membrane chloride permeability defect in polarized cystic fibrosis airway epithelia following retroviral-mediated gene transfer. Hum. Gene Ther.3 (3), 253–266 (1992).
   PubMed Web of Science ®Google Scholar
• Yoshimura K , RosenfeldMA, NakamuraHet al. Expression of the human cystic fibrosis transmembrane conductance regulator gene in the mouse lung after in vivo intratracheal plasmid-mediated gene transfer. Nucleic Acid Res.20 (12), 3233–3240 (1992).
   PubMed Web of Science ®Google Scholar
• Hyde SC , GillDR, HigginsCFet al. Correction of the ion transport defect in cystic fibrosis transgenic mice by gene therapy. Nature362 (6417), 250–255 (1993).
   PubMed Web of Science ®Google Scholar
• Zabner J , CoutureLA, GregoryRJ, GrahamSM, SmithAE, WelshMJ. Adenovirus-mediated gene transfer transiently corrects the chloride transport defect in nasal epithelia of patients with cystic fibrosis. Cell75 (2), 207–216 (1993).
   PubMed Web of Science ®Google Scholar
• Caplen NJ , GaoX, HayesPet al. Gene therapy for cystic fibrosis in humans by liposome-mediated DNA transfer: the production of resources and the regulatory process. Gene Ther.1 (2), 139–147 (1994).
   PubMed Web of Science ®Google Scholar
• Johnson LG . Gene therapy for cystic fibrosis. Chest107 (2 Suppl.), 77S–83S (1995).
   PubMed Web of Science ®Google Scholar
• Lehrman S . Virus treatment questioned after gene therapy death. Nature401 (6753), 517–518 (1999).
   PubMed Web of Science ®Google Scholar
• Horsley AR , DaviesJC, GrayRD, MacleodKA, DonovanJ, AzizZA, BellNJ, RainerM, Mt-IsaS, VoaseN, DewarMH, SaundersC, GibsonJS, Parra-LeitonJ, LarsenMD, JeswietS, SoussiS, BakarY, MeisterMG, TylerP, DohertyA, HansellDM, AshbyD, HydeSC, GillDR, GreeningAP, PorteousDJ, InnesJA, BoydAC, GriesenbachU, CunninghamS, AltonEW. Changes in physiological, functional and structural markers of cystic fibrosis lung disease with treatment of a pulmonary exacerbation. Thorax68 (6),  532–539 (2013).
   PubMed Web of Science ®Google Scholar
• Kent L , ReixP, InnesJAet al. Lung clearance index: evidence for use in clinical trials in cystic fibrosis. J. Cyst. Fibros.13 (2), 123–138 (2014).
   PubMed Web of Science ®Google Scholar
• Alton EW , BoydAC, ChengSHet al. A randomised, double-blind, placebo-controlled Phase IIb clinical trial of repeated application of gene therapy in patients with cystic fibrosis. Thorax68 (11), 1075–1077 (2013).
   PubMed Web of Science ®Google Scholar
• Junkins RD , McCormickC, LinTJ. The emerging potential of autophagy-based therapies in the treatment of cystic fibrosis lung infections. Autophagy10 (3), 538–547 (2014).
   PubMed Web of Science ®Google Scholar
• Lee TW , SouthernKW. Topical cystic fibrosis transmembrane conductance regulator gene replacement for cystic fibrosis-related lung disease. Cochrane Database Syst Rev.11, CD005599 (2013).
   Google Scholar