Local and systemic tolerability of a 2′O-methoxyethyl antisense oligonucleotide targeting interleukin-4 receptor-α delivery by inhalation in mouse and monkey

Inhalation Toxicology

Volumn 26, Issue 8, 2014, Pages 452-463

  Fey, Robert A ^a   Templin, Michael V ^a   McDonald, Jacob D ^b   Yu, Rosie Z ^a   Hutt, Julie A ^b   Gigliotti, Andrew P ^b   Henry, Scott P ^b   Reed, Matthew D ^b  

^a ISIS PHARMACEUTICALS   (United States)

^b LOVELACE RESPIRATORY RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2' O METHOXYETHYL ANTISENSE OLIGONUCLEOTIDE; ANTISENSE OLIGONUCLEOTIDE; CYTOKINE; INTERLEUKIN 13; INTERLEUKIN 4; INTERLEUKIN 4 RECEPTOR ALPHA; ISIS 231894; ISIS 369645; MESSENGER RNA; RNA; UNCLASSIFIED DRUG; CELL SURFACE RECEPTOR; IL4RA PROTEIN, MOUSE; OLIGONUCLEOTIDE;

AEROSOL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; ASTHMA; CONTROLLED STUDY; CYTOKINE RELEASE; DOSE CALCULATION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG TARGETING; DRUG TOLERABILITY; FEMALE; HAPLORHINI; HISTOPATHOLOGY; IMMUNE SYSTEM; INFLAMMATION; LUNG; LYMPH NODE; MACROPHAGE; MALE; MOUSE; NONHUMAN; PRIMATE; PRIORITY JOURNAL; PROTEIN EXPRESSION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA DEGRADATION; TOXICITY TESTING; TOXICOKINETICS; TRACHEOBRONCHIAL TREE; ANIMAL; BLOOD; DRUG EFFECTS; GENETICS; MACACA; METABOLISM; PATHOLOGY; PHYSIOLOGY; TOXICITY;

ANIMALS; FEMALE; LUNG; MACACA; MALE; MICE; OLIGONUCLEOTIDES; OLIGONUCLEOTIDES, ANTISENSE; RECEPTORS, CELL SURFACE; RNA, MESSENGER;

EID: 84903987708     PISSN: 08958378     EISSN: 10917691     Source Type: Journal    
DOI: 10.3109/08958378.2014.907587     Document Type: Article

References (31)

1. Barik S. (2005). Silence of the transcripts: RNA interference in medicine. J Mol Med 83:764-73. (Pubitemid 41407860)
2. Bide RW, Armour SJ, Yee E. (2000). Allometric respiration/body mass data for animals to be used for estimates of inhalation toxicity to young adult humans. J Appl Toxicol 20:273-90. (Pubitemid 30601407)
3. Barnes PJ. (2012). Severe asthma: advances in current management and future therapy. J Allergy Clin Immunol 129:48-59.
4. Bregman CL, Adler RR, Morton DG, et al. (2003). Recommended tissue list for histopathologic examination in repeat-dose toxicity and carcinogenicity studies: a proposal of the society of toxicologic pathology (STP). Toxicol Pathol 2:252-3. (Pubitemid 36374016)
5. Burger GT, Renne RA, Sagartz JW, et al. (1989). Histologic changes in the respiratory tract induced by inhalation of xenobiotics: physiologic adaptation or toxicity? Toxicol Appl Pharmacol 101:521-42. (Pubitemid 20027781)
6. Butler M, Stecker K, Bennett CF. (1997). Cellular distribution of phosphorothioate oligodeoxynucleotides in normal rodent tissues. Lab Invest 77:379-88. (Pubitemid 27465599)
7. Chatila TA. (2004). Interleukin-4 receptor signaling pathways in asthma pathogenesis. Trends Mol Med 10:493-9. (Pubitemid 39303622)
8. Clinical Trials.gov Identifier NCT00658749, 24 June 2009. A phase 1 study of AIR645 in healthy subjects and subjects with controlled asthma (AIR645-CS1). Available from: http://clinicaltrials.gov. [Last accessed: 6 Jan 2014].
9. Clinical Trials.gov Identifier NCT00941577, 21 July 2010. Study evaluating the effects of AIR645 on allergen-induced airway responses in subjects with mild atopic asthma. Available from: http://clinicaltrials.gov. [Last accessed: 6 Jan 2014].
10. Crosby JR, Guha M, Tung D, et al. (2007). Inhaled CD86 antisense oligonucleotide suppresses pulmonary inflammation and airway hyper-responsiveness in allergic mice. J Pharmacol Exp Ther 321: 938-46. (Pubitemid 46762701)
11. Cross S. (2001). Asthma inhalation delivery systems: the patient's viewpoint. J Aerosol Med 14:S3-7. (Pubitemid 32172848)
12. Fanta CH. (2009). Asthma (a review). N Engl J Med 360:1002-14.
13. Farman CA, Kornbrust DJ. (2003). Oligodeoxynucleotide studies in primates: antisense and immune stimulatory indications. Toxicol Pathol 31:119-22. (Pubitemid 36169411)
14. Gauvreau GM, Boulet LP, Cockcroft DW, et al. (2008). Antisense therapy against CCR3 and the common beta chain attenuates allergeninduced eosinophilic responses. Am J Respir Crit Care Med 177: 952-8. (Pubitemid 351717588)
15. Guimond A, Viau E, Aubé P, et al. (2008). Advantageous toxicity profile of inhaled antisense oligonucleotides following chronic dosing in nonhuman primates. Pulm Pharmacol Ther 21:845-54.
16. Henry SP, Giclas PC, Leeds J, et al. (1997). Activation of the alternative pathway of complement by a phosphorothioate oligonucleotide: potential mechanism of action. J Pharmacol Exp Ther 281:810-16. (Pubitemid 27203815)
17. Henry SP, Templin MV, Gillett N, et al. (1999). Correlation of toxicity and pharmacokinetic properties of a phosphorothioate oligonucleotide designed to inhibit ICAM-1. Toxicol Pathol 27:95-100. (Pubitemid 29075751)
18. Henry SP, Johnson M, Zanardi TA, et al. (2012). Renal uptake and tolerability of a 20-O-methoxyethyl modified antisense oligonucleotide (ISIS 113715) in monkey. Toxicology 301:13-20.
19. Hodges MR, Castelloe E, Chen A, et al. (2009). Randomized, doubleblind, placebo controlled first in human study of inhaled AIR645, an IL-4Ra oligonucleotide, in healthy volunteers. ajrccmconference 179.1-MeetingAbstracts. A3640.
20. Jason TL, Koropatnick J, Berg RW. (2004). Toxicology of antisense therapeutics. Toxicol Appl Pharmacol 201:66-83. (Pubitemid 39446327)
21. Karras JG, Crosby JR, Guha M, et al. (2007). Anti-inflammatory activity of inhaled IL-4 receptor-alpha antisense oligonucleotide in mice. Am J Respir Cell Mol Biol 36:276-85. (Pubitemid 46365278)
22. Levin A, Henry S, Monteith D, Templin M. (2001). Toxicity of antisense oligonucleotides. In: Crooke ST (ed.). Antisense drug technology: principles, strategies, and applications. New York: Marcel Dekker, Inc., 201-67.
23. Minton K. (2008). Allergy and asthma: what "drives" IL-4 versus IL-13 signalling? Nat Rev Immunol 8:166-7.
24. Nikula KJ, McCartney JE, McGovern T, et al. (2014). STP position paper: interpreting the significance of increased alveolar macrophages in rodents following inhalation of pharmaceutical materials. Toxicol Pathol 42:472-86.
25. Pakhale S, Mulpuru S, Boyd M. (2011). Optimal management of severe/refractory asthma. Clin Med Insights Circ Respir Pulm Med 5:37-47.
26. Rodrigo GJ, Rodrigo C, Hall JB. (2004). Acute asthma in adults: a review. Chest 125:1081-102. (Pubitemid 38367305)
27. Schlesinger RB. (1985). Comparative deposition of inhaled aerosols in experimental animals and humans: A review. J Toxicol Environ Health 15:197-214. (Pubitemid 15002055)
28. Tanaka M, Nyce Jonathan W. (2001). Respirable antisense oligonucleotides: a new drug class for respiratory disease. Respir Res 2:5-9. (Pubitemid 34187901)
29. Templin MV, Levin AA, Graham MJ, et al. (2000). Pharmacokinetic and toxicity profile of a phosphorothioate oligonucleotide following inhalation delivery to lung in mice. Antisense Nucleic Acid Drug Dev 10:359-68.
30. Tomkinson A, Tepper J, Morton M, et al. (2010). Inhaled vs subcutaneous effects of a dual IL-4/IL-13 antagonist in a monkey model of asthma. Allergy 65:69-77.
31. Yu RZ, Kim TW, Hong A, et al. (2007). Cross-species pharmacokinetic comparison from mouse to man of a second-generation antisense oligonucleotide, ISIS 301012, targeting human apolipoprotein B-100. Drug Metab Dispos 35:460-8. (Pubitemid 46333910)