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Investigation into the mechanism(s) that leads to platelet decreases in cynomolgus monkeys during administration of ISIS-104838, a 2'-MOE-modified antisense oligonucleotide.

Narayanan PK, Shen L, Curtis BR, Bourdon M, Nolan JP, Zhou F, Christian B, Gupta S, Schaubhut JL, Greenlee S, Hoffmaster C, Burel S, Witztum JL, Engelhardt JA, Henry SP.

Toxicol Sci. 2018 May 29. doi: 10.1093/toxsci/kfy119. [Epub ahead of print]


Chronic Toxicity Assessment of 2'-O-Methoxyethyl Antisense Oligonucleotides in Mice.

Zanardi TA, Kim TW, Shen L, Serota D, Papagiannis C, Park SY, Kim Y, Henry SP.

Nucleic Acid Ther. 2018 Apr 30. doi: 10.1089/nat.2017.0706. [Epub ahead of print]


2'-O-(2-Methoxyethyl) Nucleosides Are Not Phosphorylated or Incorporated Into the Genome of Human Lymphoblastoid TK6 Cells.

Saleh AF, Bachman M, Priestley CC, Gooderham NJ, Andersson P, Henry SP, Edmunds NJ, Fellows MD.

Toxicol Sci. 2018 May 1;163(1):70-78. doi: 10.1093/toxsci/kfy005.


Assessment of the Drug Interaction Potential of Unconjugated and GalNAc3-Conjugated 2'-MOE-ASOs.

Shemesh CS, Yu RZ, Warren MS, Liu M, Jahic M, Nichols B, Post N, Lin S, Norris DA, Hurh E, Huang J, Watanabe T, Henry SP, Wang Y.

Mol Ther Nucleic Acids. 2017 Dec 15;9:34-47. doi: 10.1016/j.omtn.2017.08.012. Epub 2017 Aug 30.


Reduction in ocular complement factor B protein in mice and monkeys by systemic administration of factor B antisense oligonucleotide.

Grossman TR, Carrer M, Shen L, Johnson RB, Hettrick LA, Henry SP, Monia BP, McCaleb ML.

Mol Vis. 2017 Aug 10;23:561-571. eCollection 2017.


Assessment of the Effects of 2'-Methoxyethyl Antisense Oligonucleotides on Platelet Count in Cynomolgus Nonhuman Primates.

Henry SP, Narayanan P, Shen L, Bhanot S, Younis HS, Burel SA.

Nucleic Acid Ther. 2017 Aug;27(4):197-208. doi: 10.1089/nat.2017.0666. Epub 2017 May 25.


Disposition and Pharmacokinetics of a GalNAc3-Conjugated Antisense Oligonucleotide Targeting Human Lipoprotein (a) in Monkeys.

Yu RZ, Gunawan R, Post N, Zanardi T, Hall S, Burkey J, Kim TW, Graham MJ, Prakash TP, Seth PP, Swayze EE, Geary RS, Henry SP, Wang Y.

Nucleic Acid Ther. 2016 Dec;26(6):372-380. Epub 2016 Aug 8.


SOX9 directly Regulates CTGF/CCN2 Transcription in Growth Plate Chondrocytes and in Nucleus Pulposus Cells of Intervertebral Disc.

Oh CD, Yasuda H, Zhao W, Henry SP, Zhang Z, Xue M, de Crombrugghe B, Chen D.

Sci Rep. 2016 Jul 20;6:29916. doi: 10.1038/srep29916.


Integrated Safety Assessment of 2'-O-Methoxyethyl Chimeric Antisense Oligonucleotides in NonHuman Primates and Healthy Human Volunteers.

Crooke ST, Baker BF, Kwoh TJ, Cheng W, Schulz DJ, Xia S, Salgado N, Bui HH, Hart CE, Burel SA, Younis HS, Geary RS, Henry SP, Bhanot S.

Mol Ther. 2016 Oct;24(10):1771-1782. doi: 10.1038/mt.2016.136. Epub 2016 Jun 30.


Elucidation of the Biotransformation Pathways of a Galnac3-conjugated Antisense Oligonucleotide in Rats and Monkeys.

Shemesh CS, Yu RZ, Gaus HJ, Greenlee S, Post N, Schmidt K, Migawa MT, Seth PP, Zanardi TA, Prakash TP, Swayze EE, Henry SP, Wang Y.

Mol Ther Nucleic Acids. 2016 May 10;5:e319. doi: 10.1038/mtna.2016.31.


Effects of Repeated Complement Activation Associated with Chronic Treatment of Cynomolgus Monkeys with 2'-O-Methoxyethyl Modified Antisense Oligonucleotide.

Shen L, Engelhardt JA, Hung G, Yee J, Kikkawa R, Matson J, Tayefeh B, Machemer T, Giclas PC, Henry SP.

Nucleic Acid Ther. 2016 Aug;26(4):236-49. doi: 10.1089/nat.2015.0584. Epub 2016 May 3.


Pharmacokinetic and Pharmacodynamic Investigations of ION-353382, a Model Antisense Oligonucleotide: Using Alpha-2-Macroglobulin and Murinoglobulin Double-Knockout Mice.

Shemesh CS, Yu RZ, Gaus HJ, Seth PP, Swayze EE, Bennett FC, Geary RS, Henry SP, Wang Y.

Nucleic Acid Ther. 2016 Aug;26(4):223-35. doi: 10.1089/nat.2016.0607. Epub 2016 Mar 31.


Considerations for the Characterization and Interpretation of Results Related to Alternative Complement Activation in Monkeys Associated with Oligonucleotide-Based Therapeutics.

Henry SP, Seguin R, Cavagnaro J, Berman C, Tepper J, Kornbrust D.

Nucleic Acid Ther. 2016 Aug;26(4):210-5. doi: 10.1089/nat.2015.0593. Epub 2016 Mar 16. Review.


Lack of Interactions Between an Antisense Oligonucleotide with 2'-O-(2-Methoxyethyl) Modifications and Major Drug Transporters.

Yu RZ, Warren MS, Watanabe T, Nichols B, Jahic M, Huang J, Burkey J, Geary RS, Henry SP, Wang Y.

Nucleic Acid Ther. 2016 Apr;26(2):111-7. doi: 10.1089/nat.2015.0588. Epub 2016 Mar 9.


Hepatotoxicity of high affinity gapmer antisense oligonucleotides is mediated by RNase H1 dependent promiscuous reduction of very long pre-mRNA transcripts.

Burel SA, Hart CE, Cauntay P, Hsiao J, Machemer T, Katz M, Watt A, Bui HH, Younis H, Sabripour M, Freier SM, Hung G, Dan A, Prakash TP, Seth PP, Swayze EE, Bennett CF, Crooke ST, Henry SP.

Nucleic Acids Res. 2016 Mar 18;44(5):2093-109. doi: 10.1093/nar/gkv1210. Epub 2015 Nov 8.


Inhibition of the alternative complement pathway by antisense oligonucleotides targeting complement factor B improves lupus nephritis in mice.

Grossman TR, Hettrick LA, Johnson RB, Hung G, Peralta R, Watt A, Henry SP, Adamson P, Monia BP, McCaleb ML.

Immunobiology. 2016 Jun;221(6):701-8. doi: 10.1016/j.imbio.2015.08.001. Epub 2015 Aug 10.


Scientific and Regulatory Policy Committee Points-to-consider Paper*: Drug-induced Vascular Injury Associated with Nonsmall Molecule Therapeutics in Preclinical Development: Part I. Biotherapeutics.

Frazier KS, Engelhardt JA, Fant P, Guionaud S, Henry SP, Leach MW, Louden C, Scicchitano MS, Weaver JL, Zabka TS; Society of Toxicologic Pathology Vascular Injury Working Group.

Toxicol Pathol. 2015 Oct;43(7):915-34. doi: 10.1177/0192623315570340. Epub 2015 Feb 26. Review.


Scientific and Regulatory Policy Committee Points-to-consider Paper*: Drug-induced Vascular Injury Associated with Nonsmall Molecule Therapeutics in Preclinical Development: Part 2. Antisense Oligonucleotides.

Engelhardt JA, Fant P, Guionaud S, Henry SP, Leach MW, Louden C, Scicchitano MS, Weaver JL, Zabka TS, Frazier KS; Society of Toxicologic Pathology Vascular Injury Working Group.

Toxicol Pathol. 2015 Oct;43(7):935-44. doi: 10.1177/0192623315570341. Epub 2015 Feb 24. Review.


Predictive dose-based estimation of systemic exposure multiples in mouse and monkey relative to human for antisense oligonucleotides with 2'-o-(2-methoxyethyl) modifications.

Yu RZ, Grundy JS, Henry SP, Kim TW, Norris DA, Burkey J, Wang Y, Vick A, Geary RS.

Mol Ther Nucleic Acids. 2015 Jan 20;4:e218. doi: 10.1038/mtna.2014.69.


Mechanistic understanding for the greater sensitivity of monkeys to antisense oligonucleotide-mediated complement activation compared with humans.

Shen L, Frazer-Abel A, Reynolds PR, Giclas PC, Chappell A, Pangburn MK, Younis H, Henry SP.

J Pharmacol Exp Ther. 2014 Dec;351(3):709-17. doi: 10.1124/jpet.114.219378. Epub 2014 Oct 9.


Mechanism of alternative complement pathway dysregulation by a phosphorothioate oligonucleotide in monkey and human serum.

Henry SP, Jagels MA, Hugli TE, Manalili S, Geary RS, Giclas PC, Levin AA.

Nucleic Acid Ther. 2014 Oct;24(5):326-35. doi: 10.1089/nat.2014.0491. Epub 2014 Aug 5.


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

Fey RA, Templin MV, McDonald JD, Yu RZ, Hutt JA, Gigliotti AP, Henry SP, Reed MD.

Inhal Toxicol. 2014 Jul;26(8):452-63. doi: 10.3109/08958378.2014.907587. Epub 2014 Jun 16.


Inhibiting C-reactive protein for the treatment of cardiovascular disease: promising evidence from rodent models.

Szalai AJ, McCrory MA, Xing D, Hage FG, Miller A, Oparil S, Chen YF, Mazzone M, Early R, Henry SP, Zanardi TA, Graham MJ, Crooke RM.

Mediators Inflamm. 2014;2014:353614. doi: 10.1155/2014/353614. Epub 2014 Apr 2.


Pharmacology of a central nervous system delivered 2'-O-methoxyethyl-modified survival of motor neuron splicing oligonucleotide in mice and nonhuman primates.

Rigo F, Chun SJ, Norris DA, Hung G, Lee S, Matson J, Fey RA, Gaus H, Hua Y, Grundy JS, Krainer AR, Henry SP, Bennett CF.

J Pharmacol Exp Ther. 2014 Jul;350(1):46-55. doi: 10.1124/jpet.113.212407. Epub 2014 Apr 30.


Antisense oligonucleotides on neurobehavior, respiratory, and cardiovascular function, and hERG channel current studies.

Kim TW, Kim KS, Seo JW, Park SY, Henry SP.

J Pharmacol Toxicol Methods. 2014 Jan-Feb;69(1):49-60. doi: 10.1016/j.vascn.2013.10.005. Epub 2013 Nov 8.


Preclinical evaluation of the toxicological effects of a novel constrained ethyl modified antisense compound targeting signal transducer and activator of transcription 3 in mice and cynomolgus monkeys.

Burel SA, Han SR, Lee HS, Norris DA, Lee BS, Machemer T, Park SY, Zhou T, He G, Kim Y, MacLeod AR, Monia BP, Lio S, Kim TW, Henry SP.

Nucleic Acid Ther. 2013 Jun;23(3):213-27. doi: 10.1089/nat.2013.0422.


Assessing unintended hybridization-induced biological effects of oligonucleotides.

Lindow M, Vornlocher HP, Riley D, Kornbrust DJ, Burchard J, Whiteley LO, Kamens J, Thompson JD, Nochur S, Younis H, Bartz S, Parry J, Ferrari N, Henry SP, Levin AA.

Nat Biotechnol. 2012 Oct;30(10):920-3. doi: 10.1038/nbt.2376. No abstract available.


Pharmacodynamics and subchronic toxicity in mice and monkeys of ISIS 388626, a second-generation antisense oligonucleotide that targets human sodium glucose cotransporter 2.

Zanardi TA, Han SC, Jeong EJ, Rime S, Yu RZ, Chakravarty K, Henry SP.

J Pharmacol Exp Ther. 2012 Nov;343(2):489-96. doi: 10.1124/jpet.112.197426. Epub 2012 Aug 22.


The postnatal role of Sox9 in cartilage.

Henry SP, Liang S, Akdemir KC, de Crombrugghe B.

J Bone Miner Res. 2012 Dec;27(12):2511-25. doi: 10.1002/jbmr.1696.


Renal uptake and tolerability of a 2'-O-methoxyethyl modified antisense oligonucleotide (ISIS 113715) in monkey.

Henry SP, Johnson M, Zanardi TA, Fey R, Auyeung D, Lappin PB, Levin AA.

Toxicology. 2012 Nov 15;301(1-3):13-20. doi: 10.1016/j.tox.2012.06.005. Epub 2012 Jun 16.


Unique O-methoxyethyl ribose-DNA chimeric oligonucleotide induces an atypical melanoma differentiation-associated gene 5-dependent induction of type I interferon response.

Burel SA, Machemer T, Ragone FL, Kato H, Cauntay P, Greenlee S, Salim A, Gaarde WA, Hung G, Peralta R, Freier SM, Henry SP.

J Pharmacol Exp Ther. 2012 Jul;342(1):150-62. doi: 10.1124/jpet.112.193789. Epub 2012 Apr 13.


Antisense inhibition of coagulation factor XI prolongs APTT without increased bleeding risk in cynomolgus monkeys.

Younis HS, Crosby J, Huh JI, Lee HS, Rime S, Monia B, Henry SP.

Blood. 2012 Mar 8;119(10):2401-8. doi: 10.1182/blood-2011-10-387134. Epub 2012 Jan 13.


Expression of master regulatory genes controlling skeletal development in benign cartilage and bone forming tumors.

Dancer JY, Henry SP, Bondaruk J, Lee S, Ayala AG, de Crombrugghe B, Czerniak B.

Hum Pathol. 2010 Dec;41(12):1788-93. doi: 10.1016/j.humpath.2010.06.008.


Antisense oligonucleotide therapy in diabetic retinopathy.

Hnik P, Boyer DS, Grillone LR, Clement JG, Henry SP, Green EA.

J Diabetes Sci Technol. 2009 Jul 1;3(4):924-30. Review.


Phenotypic characterization of epiphycan-deficient and epiphycan/biglycan double-deficient mice.

Nuka S, Zhou W, Henry SP, Gendron CM, Schultz JB, Shinomura T, Johnson J, Wang Y, Keene DR, Ramírez-Solis R, Behringer RR, Young MF, Höök M.

Osteoarthritis Cartilage. 2010 Jan;18(1):88-96. doi: 10.1016/j.joca.2009.11.006. Epub 2009 Nov 18.


Generation of aggrecan-CreERT2 knockin mice for inducible Cre activity in adult cartilage.

Henry SP, Jang CW, Deng JM, Zhang Z, Behringer RR, de Crombrugghe B.

Genesis. 2009 Dec;47(12):805-14. doi: 10.1002/dvg.20564.


Assessment of the effects of ISIS 2302, an anti-sense inhibitor of human ICAM-1, on cellular and humoral immunity in mice.

Henry SP, Levin AA, White K, Mennear JH.

J Immunotoxicol. 2006 Dec 1;3(4):199-211. doi: 10.1080/15476910601046538.


CpG and Non-CpG oligodeoxynucleotides induce differential proinflammatory gene expression profiles in liver and peripheral blood leukocytes in mice.

Younis HS, Vickers T, Levin AA, Henry SP.

J Immunotoxicol. 2006 Jul 1;3(2):57-68. doi: 10.1080/15476910600718236.


Effects of an antisense oligonucleotide inhibitor of human ICAM-1 on fetal development in rabbits.

Henry SP, Denny KH, Templin MV, Yu RZ, Levin AA.

Birth Defects Res B Dev Reprod Toxicol. 2004 Dec;71(6):368-73.


Effects of human and murine antisense oligonucleotide inhibitors of ICAM-1 on reproductive performance, fetal development, and post-natal development in mice.

Henry SP, Denny KH, Templin MV, Yu RZ, Levin AA.

Birth Defects Res B Dev Reprod Toxicol. 2004 Dec;71(6):359-67.


Setting sights on the treatment of ocular angiogenesis using antisense oligonucleotides.

Henry SP, Marcusson EG, Vincent TM, Dean NM.

Trends Pharmacol Sci. 2004 Oct;25(10):523-7. Review.


Pharmacokinetics of a tumor necrosis factor-alpha phosphorothioate 2'-O-(2-methoxyethyl) modified antisense oligonucleotide: comparison across species.

Geary RS, Yu RZ, Watanabe T, Henry SP, Hardee GE, Chappell A, Matson J, Sasmor H, Cummins L, Levin AA.

Drug Metab Dispos. 2003 Nov;31(11):1419-28.


Complement activation is responsible for acute toxicities in rhesus monkeys treated with a phosphorothioate oligodeoxynucleotide.

Henry SP, Beattie G, Yeh G, Chappel A, Giclas P, Mortari A, Jagels MA, Kornbrust DJ, Levin AA.

Int Immunopharmacol. 2002 Nov;2(12):1657-66.


Fomivirsen: clinical pharmacology and potential drug interactions.

Geary RS, Henry SP, Grillone LR.

Clin Pharmacokinet. 2002;41(4):255-60. Review.


Assessment of the genotoxic potential of ISIS 2302: a phosphorothioate oligodeoxynucleotide.

Henry SP, Monteith DK, Matson JE, Mathison BH, Loveday KS, Winegar RA, Matson JE, Lee PS, Riccio ES, Bakke JP, Levin AA.

Mutagenesis. 2002 May;17(3):201-9.


Drug properties of second-generation antisense oligonucleotides: how do they measure up to their predecessors?

Henry SP, Geary RS, Yu R, Levin AA.

Curr Opin Investig Drugs. 2001 Oct;2(10):1444-9.


Antiviral activity and ocular kinetics of antisense oligonucleotides designed to inhibit CMV replication.

Henry SP, Miner RC, Drew WL, Fitchett J, York-Defalco C, Rapp LM, Levin AA.

Invest Ophthalmol Vis Sci. 2001 Oct;42(11):2646-51.


Structure, chromosomal location, and tissue-specific expression of the mouse opticin gene.

Takanosu M, Boyd TC, Le Goff M, Henry SP, Zhang Y, Bishop PN, Mayne R.

Invest Ophthalmol Vis Sci. 2001 Sep;42(10):2202-10.


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