{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T05:04:46Z","timestamp":1793941486447,"version":"4.8.0"},"reference-count":30,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2016,5,1]],"date-time":"2016-05-01T00:00:00Z","timestamp":1462060800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2016,5,1]],"date-time":"2016-05-01T00:00:00Z","timestamp":1462060800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"content-domain":{"domain":["jpet.aspetjournals.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"published-print":{"date-parts":[[2016,5]]},"DOI":"10.1124\/jpet.115.230300","type":"journal-article","created":{"date-parts":[[2016,2,24]],"date-time":"2016-02-24T04:39:01Z","timestamp":1456288741000},"page":"320-330","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":29,"title":["Comparative Characterization of Hepatic Distribution and mRNA Reduction of Antisense Oligonucleotides Conjugated with Triantennary N-Acetyl Galactosamine and Lipophilic Ligands Targeting Apolipoprotein B"],"prefix":"10.1016","volume":"357","author":[{"given":"Ayahisa","family":"Watanabe","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mado","family":"Nakajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Kasuya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reina","family":"Onishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naohisa","family":"Kitade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Mayumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Ikehara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Kugimiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1124\/jpet.115.230300_bib1","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1021\/bc200235q","article-title":"Multivalent cyclic RGD conjugates for targeted delivery of small interfering RNA","volume":"22","author":"Alam","year":"2011","journal-title":"Bioconjug Chem"},{"key":"10.1124\/jpet.115.230300_bib2","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1042\/bj3400783","article-title":"Targeted delivery of oligodeoxynucleotides to parenchymal liver cells in vivo","volume":"340","author":"Biessen","year":"1999","journal-title":"Biochem J"},{"key":"10.1124\/jpet.115.230300_bib3","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1093\/nar\/28.14.2717","article-title":"Modulation of plasma protein binding and in vivo liver cell uptake of phosphorothioate oligodeoxynucleotides by cholesterol conjugation","volume":"28","author":"Bijsterbosch","year":"2000","journal-title":"Nucleic Acids Res"},{"key":"10.1124\/jpet.115.230300_bib4","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/j.jpba.2012.06.022","article-title":"Development and validation of LC-MS\/MS method for the detection and quantification of CpG oligonucleotides 107 (CpG ODN107) and its metabolites in mice plasma","volume":"70","author":"Cen","year":"2012","journal-title":"J Pharm Biomed Anal"},{"key":"10.1124\/jpet.115.230300_bib5","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/S0022-3565(25)12951-0","article-title":"Pharmacokinetic properties of several novel oligonucleotide analogs in mice","volume":"277","author":"Crooke","year":"1996","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/jpet.115.230300_bib6","doi-asserted-by":"crossref","first-page":"G709","DOI":"10.1152\/ajpgi.00451.2010","article-title":"Therapeutic targets in liver fibrosis","volume":"300","author":"Fallowfield","year":"2011","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"10.1124\/jpet.115.230300_bib7","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1177\/0192623314551840","article-title":"Antisense oligonucleotide therapies: the promise and the challenges from a toxicologic pathologist\u2019s perspective","volume":"43","author":"Frazier","year":"2015","journal-title":"Toxicol Pathol"},{"key":"10.1124\/jpet.115.230300_bib8","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/S0022-3565(24)37605-0","article-title":"In vivo distribution and metabolism of a phosphorothioate oligonucleotide within rat liver after intravenous administration","volume":"286","author":"Graham","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"10.1124\/jpet.115.230300_bib9","doi-asserted-by":"crossref","first-page":"235","DOI":"10.2165\/00063030-200721040-00004","article-title":"Locked nucleic acid oligonucleotides: the next generation of antisense agents?","volume":"21","author":"Gr\u00fcnweller","year":"2007","journal-title":"BioDrugs"},{"key":"10.1124\/jpet.115.230300_bib10","doi-asserted-by":"crossref","first-page":"3185","DOI":"10.1093\/nar\/gkg409","article-title":"Comparison of different antisense strategies in mammalian cells using locked nucleic acids, 2\u2032-O-methyl RNA, phosphorothioates and small interfering RNA","volume":"31","author":"Gr\u00fcnweller","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"10.1124\/jpet.115.230300_bib11","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.4049\/jimmunol.1202733","article-title":"Histones activate the NLRP3 inflammasome in Kupffer cells during sterile inflammatory liver injury","volume":"191","author":"Huang","year":"2013","journal-title":"J Immunol"},{"key":"10.1124\/jpet.115.230300_bib12","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0891-5849(92)90166-E","article-title":"Tolerance and safety of vitamin E: a toxicological position report","volume":"13","author":"Kappus","year":"1992","journal-title":"Free Radic Biol Med"},{"key":"10.1124\/jpet.115.230300_bib13","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/S1472-6483(10)61851-2","article-title":"Efficacy of 2-methoxyethoxy-modified antisense oligonucleotides for the study of mouse preimplantation development","volume":"6","author":"Kimber","year":"2003","journal-title":"Reprod Biomed Online"},{"key":"10.1124\/jpet.115.230300_bib14","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1038\/nbt.3078","article-title":"Efficient delivery of RNAi prodrugs containing reversible charge-neutralizing phosphotriester backbone modifications","volume":"32","author":"Meade","year":"2014","journal-title":"Nat Biotechnol"},{"key":"10.1124\/jpet.115.230300_bib15","doi-asserted-by":"crossref","first-page":"16958","DOI":"10.1021\/ja505986a","article-title":"Multivalent N-acetylgalactosamine-conjugated siRNA localizes in hepatocytes and elicits robust RNAi-mediated gene silencing","volume":"136","author":"Nair","year":"2014","journal-title":"J Am Chem Soc"},{"key":"10.1124\/jpet.115.230300_bib16","doi-asserted-by":"crossref","first-page":"7969","DOI":"10.1038\/ncomms8969","article-title":"DNA\/RNA heteroduplex oligonucleotide for highly efficient gene silencing","volume":"6","author":"Nishina","year":"2015","journal-title":"Nat Commun"},{"key":"10.1124\/jpet.115.230300_bib17","doi-asserted-by":"crossref","first-page":"e220","DOI":"10.1038\/mtna.2014.72","article-title":"Chimeric antisense oligonucleotide conjugated to \u03b1-tocopherol","volume":"4","author":"Nishina","year":"2015","journal-title":"Mol Ther Nucleic Acids"},{"key":"10.1124\/jpet.115.230300_bib18","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.2116\/analsci.31.1255","article-title":"Surface plasmon resonance assay of binding properties of antisense oligonucleotides to serum albumins and lipoproteins","volume":"31","author":"Onishi","year":"2015","journal-title":"Anal Sci"},{"key":"10.1124\/jpet.115.230300_bib19","doi-asserted-by":"crossref","first-page":"12829","DOI":"10.1016\/S0021-9258(18)98766-1","article-title":"Evidence that the nonparenchymal cells of the liver are the principal source of cholesteryl ester transfer protein in primates","volume":"266","author":"Pape","year":"1991","journal-title":"J Biol Chem"},{"key":"10.1124\/jpet.115.230300_bib20","doi-asserted-by":"crossref","first-page":"8796","DOI":"10.1093\/nar\/gku531","article-title":"Targeted delivery of antisense oligonucleotides to hepatocytes using triantennary N-acetyl galactosamine improves potency 10-fold in mice","volume":"42","author":"Prakash","year":"2014","journal-title":"Nucleic Acids Res"},{"key":"10.1124\/jpet.115.230300_bib21","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/S0889-8588(02)00005-9","article-title":"Reticulocyte analysis by flow cytometry and other techniques","volume":"16","author":"Riley","year":"2002","journal-title":"Hematol Oncol Clin North Am"},{"key":"10.1124\/jpet.115.230300_bib22","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1016\/j.jhep.2013.05.045","article-title":"Liver as a target for oligonucleotide therapeutics","volume":"59","author":"Sehgal","year":"2013","journal-title":"J Hepatol"},{"key":"10.1124\/jpet.115.230300_bib23","doi-asserted-by":"crossref","first-page":"7100","DOI":"10.1093\/nar\/gkq457","article-title":"Short locked nucleic acid antisense oligonucleotides potently reduce apolipoprotein B mRNA and serum cholesterol in mice and non-human primates","volume":"38","author":"Straarup","year":"2010","journal-title":"Nucleic Acids Res"},{"key":"10.1124\/jpet.115.230300_bib24","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1093\/nar\/gkl1071","article-title":"Antisense oligonucleotides containing locked nucleic acid improve potency but cause significant hepatotoxicity in animals","volume":"35","author":"Swayze","year":"2007","journal-title":"Nucleic Acids Res"},{"key":"10.1124\/jpet.115.230300_bib25","doi-asserted-by":"crossref","first-page":"2354","DOI":"10.1074\/jbc.M007783200","article-title":"2\u2032-O,4\u2032-C-methylene bridged nucleic acid modification promotes pyrimidine motif triplex DNA formation at physiological pH: thermodynamic and kinetic studies","volume":"276","author":"Torigoe","year":"2001","journal-title":"J Biol Chem"},{"key":"10.1124\/jpet.115.230300_bib27","doi-asserted-by":"crossref","first-page":"e0138655","DOI":"10.1371\/journal.pone.0138655","article-title":"All-in-one: advanced preparation of human parenchymal and non-parenchymal liver cells","volume":"10","author":"Werner","year":"2015","journal-title":"PLoS One"},{"key":"10.1124\/jpet.115.230300_bib28","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1038\/nbt1339","article-title":"Mechanisms and optimization of in vivo delivery of lipophilic siRNAs","volume":"25","author":"Wolfrum","year":"2007","journal-title":"Nat Biotechnol"},{"key":"10.1124\/jpet.115.230300_bib29","first-page":"195","article-title":"Application of novel quantitative bioanalytical methods for pharmacokinetic and pharmacokinetic\/pharmacodynamic assessments of antisense oligonucleotides","volume":"7","author":"Yu","year":"2004","journal-title":"Curr Opin Drug Discov Devel"},{"key":"10.1124\/jpet.115.230300_bib30","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1517\/17425255.2013.737320","article-title":"Clinical pharmacokinetics of second generation antisense oligonucleotides","volume":"9","author":"Yu","year":"2013","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"10.1124\/jpet.115.230300_bib31","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/S0022-3565(24)38750-6","article-title":"Pharmacokinetics and pharmacodynamics of an antisense phosphorothioate oligonucleotide targeting Fas mRNA in mice","volume":"296","author":"Yu","year":"2001","journal-title":"J Pharmacol Exp Ther"}],"container-title":["The Journal of Pharmacology and Experimental Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524193056?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022356524193056?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1124\/jpet.115.230300","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T19:44:32Z","timestamp":1739994272000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022356524193056"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5]]},"references-count":30,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,5]]}},"alternative-id":["S0022356524193056"],"URL":"https:\/\/doi.org\/10.1124\/jpet.115.230300","relation":{},"ISSN":["0022-3565"],"issn-type":[{"value":"0022-3565","type":"print"}],"subject":[],"published":{"date-parts":[[2016,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Comparative Characterization of Hepatic Distribution and mRNA Reduction of Antisense Oligonucleotides Conjugated with Triantennary N-Acetyl Galactosamine and Lipophilic Ligands Targeting Apolipoprotein B","name":"articletitle","label":"Article Title"},{"value":"The Journal of Pharmacology and Experimental Therapeutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1124\/jpet.115.230300","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2016 by The American Society for Pharmacology and Experimental Therapeutics","name":"copyright","label":"Copyright"}]}}