Inhaled ENaC antisense oligonucleotide ameliorates cystic fibrosis-like lung disease in mice

Journal of Cystic Fibrosis

Volumn 16, Issue 6, 2017, Pages 671-680

  Crosby, Jeff R ^a   Zhao, Chenguang ^a   Jiang, Chong ^b   Bai, Dong ^a   Katz, Melanie ^a   Greenlee, Sarah ^a   Kawabe, Hiroshi ^c   McCaleb, Michael ^a   Rotin, Daniela ^b   Guo, Shuling ^a   Monia, Brett P ^a  

^a ISIS PHARMACEUTICALS   (United States)

^b HOSPITAL FOR SICK CHILDREN   (Canada)

^c MAX PLANCK INSTITUTE OF EXPERIMENTAL MEDICINE   (Germany)

Author keywords

Aerosol; Antisense oligonucleotide; Cystic fibrosis; ENaC

Indexed keywords

ANTIFIBROTIC AGENT; ANTISENSE OLIGONUCLEOTIDE; EPITHELIAL SODIUM CHANNEL; MESSENGER RNA; RIBONUCLEASE; RIBONUCLEASE H; UBIQUITIN PROTEIN LIGASE; UBIQUITIN PROTEIN LIGASE NEDD4; EPITHELIAL SODIUM CHANNEL BLOCKING AGENT; RESPIRATORY TRACT AGENT;

AEROSOL; AIRWAY EPITHELIUM CELL; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTISENSE THERAPY; ARTICLE; BREATHING PATTERN; CELL SURFACE; COMPARATIVE STUDY; CONTROLLED STUDY; DOWN REGULATION; DRUG EFFICACY; DRUG SAFETY; ENZYME ACTIVITY; ENZYME INHIBITION; GENE; GENETIC CODE; GOBLET CELL; ION TRANSPORT; LIMIT OF QUANTITATION; LUNG FIBROSIS; MOUSE; MOUSE MODEL; NONHUMAN; PHARMACOGENETICS; PROTEIN EXPRESSION; RNA DEGRADATION; SCNN1A GENE; ANIMAL; CYSTIC FIBROSIS; DISEASE MODEL; INHALATIONAL DRUG ADMINISTRATION; METABOLISM; PATHOPHYSIOLOGY; RESPIRATORY MUCOSA; TREATMENT OUTCOME;

ADMINISTRATION, INHALATION; ANIMALS; CYSTIC FIBROSIS; DISEASE MODELS, ANIMAL; EPITHELIAL SODIUM CHANNEL BLOCKERS; EPITHELIAL SODIUM CHANNELS; MICE; OLIGONUCLEOTIDES, ANTISENSE; RESPIRATORY MUCOSA; RESPIRATORY SYSTEM AGENTS; TREATMENT OUTCOME;

EID: 85019952794     PISSN: 15691993     EISSN: 18735010     Source Type: Journal    
DOI: 10.1016/j.jcf.2017.05.003     Document Type: Article

References (38)

1. Mall, M.A., Hartl, D., CFTR: cystic fibrosis and beyond. Eur Respir J 44 (2014), 1042–1054.
2. Kerem, B., Rommens, J.M., Buchanan, J.A., Markiewicz, D., Cox, T.K., Chakravarti, A., et al. Identification of the cystic fibrosis gene: genetic analysis. Science 245 (1989), 1073–1080.
3. Rommens, J.M., Iannuzzi, M.C., Kerem, B., Drumm, M.L., Melmer, G., Dean, M., et al. Identification of the cystic fibrosis gene: chromosome walking and jumping. Science 245 (1989), 1059–1065.
4. Rubenstein, R.C., Lockwood, S.R., Lide, E., Bauer, R., Suaud, L., Grumbach, Y., Regulation of endogenous ENaC functional expression by CFTR and DeltaF508-CFTR in airway epithelial cells. Am J Physiol Lung Cell Mol Physiol 300 (2011), L88–L101.
5. Anderson, M.P., Gregory, R.J., Thompson, S., Souza, D.W., Paul, S., Mulligan, R.C., et al. Demonstration that CFTR is a chloride channel by alteration of its anion selectivity. Science 253 (1991), 202–205.
6. Stutts, M.J., Canessa, C.M., Olsen, J.C., Hamrick, M., Cohn, J.A., Rossier, B.C., et al. CFTR as a cAMP-dependent regulator of sodium channels. Science 269 (1995), 847–850.
7. + channel. J Gen Physiol 114 (1999), 13–30.
8. + channel is made of three homologous subunits. Nature 367 (1994), 463–467.
9. Bhalla, V., Hallows, K.R., Mechanisms of ENaC regulation and clinical implications. J Am Soc Nephrol 19 (2008), 1845–1854.
10. Smith, J.J., Travis, S.M., Greenberg, E.P., Welsh, M.J., Cystic fibrosis airway epithelia fail to kill bacteria because of abnormal airway surface fluid. Cell 85 (1996), 229–236.
11. Hobbs, C.A., Da Tan, C., Tarran, R., Does epithelial sodium channel hyperactivity contribute to cystic fibrosis lung disease?. J Physiol 591 (2013), 4377–4387.
12. + absorption produces cystic fibrosis-like lung disease in mice. Nat Med 10 (2004), 487–493.
13. Kimura, T., Kawabe, H., Jiang, C., Zhang, W., Xiang, Y.Y., Lu, C., et al. Deletion of the ubiquitin ligase Nedd4L in lung epithelia causes cystic fibrosis-like disease. Proc Natl Acad Sci U S A 108 (2011), 3216–3221.
14. Boase, N.A., Rychkov, G.Y., Townley, S.L., Dinudom, A., Candi, E., Voss, A.K., et al. Respiratory distress and perinatal lethality in Nedd4-2-deficient mice. Nat Commun, 2, 2011, 287.
15. Donaldson, S.H., Bennett, W.D., Zeman, K.L., Knowles, M.R., Tarran, R., Boucher, R.C., Mucus clearance and lung function in cystic fibrosis with hypertonic saline. N Engl J Med 354 (2006), 241–250.
16. Knowles, M.R., Church, N.L., Waltner, W.E., Yankaskas, J.R., Gilligan, P., King, M., et al. A pilot study of aerosolized amiloride for the treatment of lung disease in cystic fibrosis. N Engl J Med 322 (1990), 1189–1194.
17. Zhou, Z., Treis, D., Schubert, S.C., Harm, M., Schatterny, J., Hirtz, S., et al. Preventive but not late amiloride therapy reduces morbidity and mortality of lung disease in betaENaC-overexpressing mice. Am J Respir Crit Care Med 178 (2008), 1245–1256.
18. O'Riordan, T.G., Donn, K.H., Hodsman, P., Ansede, J.H., Newcomb, T., Lewis, S.A., et al. Acute hyperkalemia associated with inhalation of a potent ENaC antagonist: phase 1 trial of GS-9411. J Aerosol Med Pulm Drug Deliv 27 (2014), 200–208.
19. Crosby, J.R., Guha, M., Tung, D., Miller, D.A., Bender, B., Condon, T.P., et al. Inhaled CD86 antisense oligonucleotide suppresses pulmonary inflammation and airway hyper-responsiveness in allergic mice. J Pharmacol Exp Ther 321 (2007), 938–946.
20. Fey, R.A., Templin, M.V., McDonald, J.D., Yu, R.Z., Hutt, J.A., Gigliotti, A.P., et al. Local and systemic tolerability of a 2'O-methoxyethyl antisense oligonucleotide targeting interleukin-4 receptor-alpha delivery by inhalation in mouse and monkey. Inhal Toxicol 26 (2014), 452–463.
21. Karras, J.G., Crosby, J.R., Guha, M., Tung, D., Miller, D.A., Gaarde, W.A., et al. Anti-inflammatory activity of inhaled IL-4 receptor-alpha antisense oligonucleotide in mice. Am J Respir Cell Mol Biol 36 (2007), 276–285.
22. Templin, M.V., Levin, A.A., Graham, M.J., Aberg, P.M., Axelsson, B.I., Butler, M., et al. Pharmacokinetic and toxicity profile of a phosphorothioate oligonucleotide following inhalation delivery to lung in mice. Antisense Nucleic Acid Drug Dev 10 (2000), 359–368.
23. Baker, B.F., Lot, S.S., Condon, T.P., Cheng-Flournoy, S., Lesnik, E.A., Sasmor, H.M., et al. 2′-O-(2-Methoxy)ethyl-modified anti-intercellular adhesion molecule 1 (ICAM-1) oligonucleotides selectively increase the ICAM-1 mRNA level and inhibit formation of the ICAM-1 translation initiation complex in human umbilical vein endothelial cells. J Biol Chem 272 (1997), 11994–12000.
24. Hamelmann, E., Schwarze, J., Takeda, K., Oshiba, A., Larsen, G.L., Irvin, C.G., et al. Noninvasive measurement of airway responsiveness in allergic mice using barometric plethysmography. Am J Respir Crit Care Med 156 (1997), 766–775.
25. Garty, H., Palmer, L.G., Epithelial sodium channels: function, structure, and regulation. Physiol Rev 77 (1997), 359–396.
26. Burgel, P.R., Bellis, G., Olesen, H.V., Viviani, L., Zolin, A., Blasi, F., et al. Future trends in cystic fibrosis demography in 34 European countries. Eur Respir J 46 (2015), 133–141.
27. Bennett, C.F., Swayze, E.E., RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Annu Rev Pharmacol Toxicol 50 (2010), 259–293.
28. Clarke, L.L., Grubb, B.R., Gabriel, S.E., Smithies, O., Koller, B.H., Boucher, R.C., Defective epithelial chloride transport in a gene-targeted mouse model of cystic fibrosis. Science 257 (1992), 1125–1128.
29. + channel. FASEB J 15 (2001), 204–214.
30. Collawn, J.F., Lazrak, A., Bebok, Z., Matalon, S., The CFTR and ENaC debate: how important is ENaC in CF lung disease?. Am J Physiol Lung Cell Mol Physiol 302 (2012), L1141–L1146.
31. Garland, A.L., Walton, W.G., Coakley, R.D., Tan, C.D., Gilmore, R.C., Hobbs, C.A., et al. Molecular basis for pH-dependent mucosal dehydration in cystic fibrosis airways. Proc Natl Acad Sci U S A 110 (2013), 15973–15978.
32. Mall, M.A., Galietta, L.J., Targeting ion channels in cystic fibrosis. J Cyst Fibros 14 (2015), 561–570.
33. + hyperabsorption in cystic fibrosis. J Gene Med 11 (2009), 813–823.
34. Jain, L., Chen, X.J., Malik, B., Al-Khalili, O., Eaton, D.C., Antisense oligonucleotides against the alpha-subunit of ENaC decrease lung epithelial cation-channel activity. Am J Physiol 276 (1999), L1046–L1051.
35. Clark, K.L., Hughes, S.A., Bulsara, P., Coates, J., Moores, K., Parry, J., et al. Pharmacological characterization of a novel ENaC alpha siRNA (GSK2225745) with potential for the treatment of cystic fibrosis. Mol Ther Nucleic Acids, 2, 2013, e65.
36. Lai, S.K., Wang, Y.Y., Hanes, J., Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv Drug Deliv Rev 61 (2009), 158–171.
37. Hodges, M.R., C.E., Chen, A., Geary, R.S., Karras, J.G., Shapiro, D., et al. Randomized, double-blind, placebo controlled first in human study of inhaled AIR645, an IL-4Ra oligonucleotide, in healthy volunteers. ajrccmconference 179.1, 2009.
38. Clancy, J.P., Rowe, S.M., Accurso, F.J., Aitken, M.L., Amin, R.S., Ashlock, M.A., 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 67 (2012), 12–18.