{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T20:50:19Z","timestamp":1789505419272,"version":"build-2803163510"},"reference-count":30,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002344","name":"Ira Sohn Research Conference Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002344","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100003287","name":"Rally Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100003287","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007028","name":"Leona M and Harry B Helmsley Charitable Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007028","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018290","name":"Bear Necessities Pediatric Cancer Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018290","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020940","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020940","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy"],"published-print":{"date-parts":[[2024,1]]},"DOI":"10.1016\/j.ymthe.2023.11.012","type":"journal-article","created":{"date-parts":[[2023,11,20]],"date-time":"2023-11-20T21:02:54Z","timestamp":1700514174000},"page":"140-151","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":21,"title":["GalNAc-conjugated siRNA targeting the DNAJB1-PRKACA fusion junction in fibrolamellar hepatocellular carcinoma"],"prefix":"10.1016","volume":"32","author":[{"given":"Christoph","family":"Neumayer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Requena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline S.","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Qureshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Vaughan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thazha P.","family":"Prakash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Revenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8615-4224","authenticated-orcid":false,"given":"Sanford M.","family":"Simon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ymthe.2023.11.012_bib1","doi-asserted-by":"crossref","DOI":"10.6064\/2012\/743790","article-title":"Fibrolamellar carcinoma: 2012 update","volume":"2012","author":"Torbenson","year":"2012","journal-title":"Scientifica"},{"key":"10.1016\/j.ymthe.2023.11.012_bib3","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1055\/s-0037-1621710","article-title":"Fibrolamellar Carcinoma: Recent Advances and Unresolved Questions on the Molecular Mechanisms","volume":"38","author":"Lalazar","year":"2018","journal-title":"Semin. Liver Dis."},{"key":"10.1016\/j.ymthe.2023.11.012_bib4","doi-asserted-by":"crossref","DOI":"10.1016\/j.currproblcancer.2021.100770","article-title":"Fibrolamellar carcinoma: An entity all its own","volume":"45","author":"O'Neill","year":"2021","journal-title":"Curr. Probl. Cancer"},{"key":"10.1016\/j.ymthe.2023.11.012_bib2","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1126\/science.1249484","article-title":"Detection of a recurrent DNAJB1-PRKACA chimeric transcript in fibrolamellar hepatocellular carcinoma","volume":"343","author":"Honeyman","year":"2014","journal-title":"Science"},{"key":"10.1016\/j.ymthe.2023.11.012_bib5","doi-asserted-by":"crossref","first-page":"S43","DOI":"10.1002\/jcph.957","article-title":"RNA Therapeutics in Oncology: Advances, Challenges, and Future Directions","volume":"57","author":"MacLeod","year":"2017","journal-title":"J.\u00a0Clin. Pharmacol."},{"key":"10.1016\/j.ymthe.2023.11.012_bib6","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/s41392-020-0207-x","article-title":"Therapeutic siRNA: state of the art","volume":"5","author":"Hu","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.ymthe.2023.11.012_bib7","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s40259-022-00549-3","article-title":"Therapeutic siRNA: State-of-the-Art and Future Perspectives","volume":"36","author":"Friedrich","year":"2022","journal-title":"BioDrugs."},{"key":"10.1016\/j.ymthe.2023.11.012_bib8","doi-asserted-by":"crossref","first-page":"13076","DOI":"10.1073\/pnas.1716483114","article-title":"DNAJB1-PRKACA fusion kinase interacts with beta-catenin and the liver regenerative response to drive fibrolamellar hepatocellular carcinoma","volume":"114","author":"Kastenhuber","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.ymthe.2023.11.012_bib9","doi-asserted-by":"crossref","first-page":"1662","DOI":"10.1053\/j.gastro.2017.09.008","article-title":"CRISPR\/Cas9 Engineering of Adult Mouse Liver Demonstrates That the Dnajb1-Prkaca Gene Fusion is Sufficient to Induce Tumors Resembling Fibrolamellar Hepatocellular Carcinoma","volume":"153","author":"Engelholm","year":"2017","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ymthe.2023.11.012_bib10","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1158\/1078-0432.CCR-22-1851","article-title":"Oncogenic Addiction of Fibrolamellar Hepatocellular Carcinoma to the Fusion Kinase DNAJB1-PRKACA","volume":"29","author":"Neumayer","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.ymthe.2023.11.012_bib11","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1111\/hepr.12599","article-title":"Variable asialoglycoprotein receptor 1 expression in liver disease: Implications for therapeutic intervention","volume":"46","author":"Witzigmann","year":"2016","journal-title":"Hepatol. Res."},{"key":"10.1016\/j.ymthe.2023.11.012_bib12","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.ymthe.2017.08.019","article-title":"Evaluation of GalNAc-siRNA Conjugate Activity in Pre-clinical Animal Models with Reduced Asialoglycoprotein Receptor Expression","volume":"26","author":"Willoughby","year":"2018","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2023.11.012_bib13","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1016\/j.ymthe.2019.06.009","article-title":"Enhanced Potency of GalNAc-Conjugated Antisense Oligonucleotides in Hepatocellular Cancer Models","volume":"27","author":"Kim","year":"2019","journal-title":"Mol. Ther."},{"key":"10.1016\/j.ymthe.2023.11.012_bib14","doi-asserted-by":"crossref","first-page":"7581","DOI":"10.1093\/nar\/gkx507","article-title":"5\u0384-Vinylphosphonate improves tissue accumulation and efficacy of conjugated siRNAs in\u00a0vivo","volume":"45","author":"Haraszti","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ymthe.2023.11.012_bib15","doi-asserted-by":"crossref","first-page":"2817","DOI":"10.1016\/j.bmcl.2016.04.063","article-title":"Synergistic effect of phosphorothioate, 5'-vinylphosphonate and GalNAc modifications for enhancing activity of synthetic siRNA","volume":"26","author":"Prakash","year":"2016","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ymthe.2023.11.012_bib16","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/s41573-021-00162-z","article-title":"Antisense technology: an overview and prospectus","volume":"20","author":"Crooke","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ymthe.2023.11.012_bib17","doi-asserted-by":"crossref","first-page":"11827","DOI":"10.1093\/nar\/gkaa670","article-title":"Investigating the pharmacodynamic durability of GalNAc-siRNA conjugates","volume":"48","author":"Brown","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ymthe.2023.11.012_bib18","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.161820","article-title":"Targeting BCL-XL in fibrolamellar hepatocellular carcinoma","volume":"7","author":"Shebl","year":"2022","journal-title":"JCI Insight"},{"key":"10.1016\/j.ymthe.2023.11.012_bib19","doi-asserted-by":"crossref","first-page":"R762","DOI":"10.1016\/j.cub.2014.06.043","article-title":"Aberrant regulation and function of microRNAs in cancer","volume":"24","author":"Adams","year":"2014","journal-title":"Curr. Biol."},{"key":"10.1016\/j.ymthe.2023.11.012_bib20","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1158\/2159-8290.CD-20-0872","article-title":"Identification of Novel Therapeutic Targets for Fibrolamellar Carcinoma Using Patient-Derived Xenografts and Direct-from-Patient Screening","volume":"11","author":"Lalazar","year":"2021","journal-title":"Cancer Discov."},{"key":"10.1016\/j.ymthe.2023.11.012_bib21","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aal5253","article-title":"Targeting KRAS-dependent tumors with AZD4785, a high-affinity therapeutic antisense oligonucleotide inhibitor of KRAS","volume":"9","author":"Ross","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ymthe.2023.11.012_bib22","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1158\/0008-5472.CAN-20-0948","article-title":"ASO-Based PKM Splice-Switching Therapy Inhibits Hepatocellular Carcinoma Growth","volume":"82","author":"Ma","year":"2022","journal-title":"Cancer Res."},{"key":"10.1016\/j.ymthe.2023.11.012_bib24","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1089\/nat.2018.0736","article-title":"GalNAc-siRNA Conjugates: Leading the Way for Delivery of RNAi Therapeutics","volume":"28","author":"Springer","year":"2018","journal-title":"Nucleic Acid Ther."},{"key":"10.1016\/j.ymthe.2023.11.012_bib25","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aam9327","article-title":"FolamiRs: Ligand-targeted, vehicle-free delivery of microRNAs for the treatment of cancer","volume":"9","author":"Orellana","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.ymthe.2023.11.012_bib26","doi-asserted-by":"crossref","DOI":"10.3390\/molecules25112692","article-title":"Lipid and Polymer-Based Nanoparticle siRNA Delivery Systems for Cancer Therapy","volume":"25","author":"Mainini","year":"2020","journal-title":"Molecules"},{"key":"10.1016\/j.ymthe.2023.11.012_bib27","doi-asserted-by":"crossref","first-page":"1082","DOI":"10.1093\/nar\/gky1239","article-title":"Diverse lipid conjugates for functional extra-hepatic siRNA delivery in\u00a0vivo","volume":"47","author":"Biscans","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.ymthe.2023.11.012_bib28","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1089\/nat.2018.0725","article-title":"Improving siRNA Delivery In\u00a0Vivo Through Lipid Conjugation","volume":"28","author":"Osborn","year":"2018","journal-title":"Nucleic Acid Ther."},{"key":"10.1016\/j.ymthe.2023.11.012_bib29","doi-asserted-by":"crossref","first-page":"1500","DOI":"10.1038\/s41587-022-01334-x","article-title":"Expanding RNAi therapeutics to extrahepatic tissues with lipophilic conjugates","volume":"40","author":"Brown","year":"2022","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.ymthe.2023.11.012_bib30","doi-asserted-by":"crossref","first-page":"2718","DOI":"10.1021\/acs.jmedchem.5b01948","article-title":"Comprehensive Structure-Activity Relationship of Triantennary N-Acetylgalactosamine Conjugated Antisense Oligonucleotides for Targeted Delivery to Hepatocytes","volume":"59","author":"Prakash","year":"2016","journal-title":"J.\u00a0Med. Chem."},{"key":"10.1016\/j.ymthe.2023.11.012_bib31","doi-asserted-by":"crossref","first-page":"E5916","DOI":"10.1073\/pnas.1424894112","article-title":"Transcriptomic characterization of fibrolamellar hepatocellular carcinoma","volume":"112","author":"Simon","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["Molecular Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001623006135?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1525001623006135?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2024,12,11]],"date-time":"2024-12-11T19:20:56Z","timestamp":1733944856000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S1525001623006135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["S1525001623006135"],"URL":"https:\/\/doi.org\/10.1016\/j.ymthe.2023.11.012","relation":{},"ISSN":["1525-0016"],"issn-type":[{"value":"1525-0016","type":"print"}],"subject":[],"published":{"date-parts":[[2024,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"GalNAc-conjugated siRNA targeting the DNAJB1-PRKACA fusion junction in fibrolamellar hepatocellular carcinoma","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ymthe.2023.11.012","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Author(s).","name":"copyright","label":"Copyright"}]}}