{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:20:55Z","timestamp":1789428055203,"version":"build-2803163510"},"reference-count":35,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy Methods & Clinical Development"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1016\/j.omtm.2025.101617","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T00:50:56Z","timestamp":1760662256000},"page":"101617","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptional changes in non-human primate tissues after intrathecal delivery of serotype 9 adeno-associated viral vector: Insights into organ toxicities"],"prefix":"10.1016","volume":"33","author":[{"given":"Fumiaki","family":"Aihara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Mardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera","family":"Ruda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony del","family":"Rio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Bigot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Singer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megumi","family":"Onishi-Seebacher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Couttet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Mansfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3654-9663","authenticated-orcid":false,"given":"Eloise","family":"Hudry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.omtm.2025.101617_bib1","first-page":"2072","article-title":"A human parvovirus, adeno-associated virus, as a eucaryotic vector: transient expression and encapsidation of the procaryotic gene for chloramphenicol acetyltransferase","volume":"4","author":"Tratschin","year":"1984","journal-title":"Mol. Cell Biol."},{"key":"10.1016\/j.omtm.2025.101617_bib2","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1073\/pnas.79.6.2077","article-title":"Cloning of adeno-associated virus into pBR322: rescue of intact virus from the recombinant plasmid in human cells","volume":"79","author":"Samulski","year":"1982","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.omtm.2025.101617_bib3","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/s41573-019-0012-9","article-title":"Adeno-associated virus vector as a platform for gene therapy delivery","volume":"18","author":"Wang","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.omtm.2025.101617_bib4","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1038\/mt.2013.226","article-title":"Birth of a new therapeutic platform: 47 years of adeno-associated virus biology from virus discovery to licensed gene therapy","volume":"21","author":"Flotte","year":"2013","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2025.101617_bib6","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/s41434-022-00363-0","article-title":"Changing trends in the development of AAV-based gene therapies: a meta-analysis of past and present therapies","volume":"30","author":"Burdett","year":"2023","journal-title":"Gene Ther."},{"key":"10.1016\/j.omtm.2025.101617_bib7","series-title":"Toxicity Risks of Adeno-Associated Virus (AAV) Vectors for Gene Therapy (GT)","year":"2021"},{"key":"10.1016\/j.omtm.2025.101617_bib8","doi-asserted-by":"crossref","DOI":"10.1016\/j.yrtph.2022.105332","article-title":"Adeno-associated virus (AAV)-based gene therapy products: What are toxicity studies in non-human primates showing us?","volume":"138","author":"Baldrick","year":"2023","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"10.1016\/j.omtm.2025.101617_bib9","doi-asserted-by":"crossref","first-page":"57","DOI":"10.2131\/jts.46.57","article-title":"Development challenges associated with rAAV-based gene therapies","volume":"46","author":"Bolt","year":"2021","journal-title":"J. Toxicol. Sci."},{"key":"10.1016\/j.omtm.2025.101617_bib10","doi-asserted-by":"crossref","first-page":"2999","DOI":"10.1016\/j.ymthe.2023.07.020","article-title":"Liver injury in cynomolgus monkeys following intravenous and intrathecal scAAV9 gene therapy delivery","volume":"31","author":"Hudry","year":"2023","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2025.101617_bib11","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.omtm.2022.12.012","article-title":"Neurofilament light chain and dorsal root ganglia injury after adeno-associated virus 9 gene therapy in nonhuman primates","volume":"28","author":"Johnson","year":"2023","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.omtm.2025.101617_bib12","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/j.ymthe.2024.02.002","article-title":"High-dose systemic adeno-associated virus vector administration causes liver and sinusoidal endothelial cell injury","volume":"32","author":"Hordeaux","year":"2024","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2025.101617_bib13","doi-asserted-by":"crossref","DOI":"10.1016\/j.omtm.2024.101296","article-title":"Subacute liver injury in two young infants following gene replacement therapy for spinal muscular atrophy","volume":"32","author":"Ables","year":"2024","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.omtm.2025.101617_bib14","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/s41434-023-00405-1","article-title":"Adeno-associated virus vectors and neurotoxicity-lessons from preclinical and human studies","volume":"32","author":"Stone","year":"2025","journal-title":"Gene Ther."},{"key":"10.1016\/j.omtm.2025.101617_bib15","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1056\/NEJMoa2307798","article-title":"Death after High-Dose rAAV9 Gene Therapy in a Patient with Duchenne's Muscular Dystrophy","volume":"389","author":"Lek","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.omtm.2025.101617_bib16","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/S1474-4422(23)00313-7","article-title":"Safety and efficacy of gene replacement therapy for X-linked myotubular myopathy (ASPIRO): a multinational, open-label, dose-escalation trial","volume":"22","author":"Shieh","year":"2023","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.omtm.2025.101617_bib17","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1089\/hum.2020.167","article-title":"Adeno-Associated Virus-Induced Dorsal Root Ganglion Pathology","volume":"31","author":"Hordeaux","year":"2020","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.omtm.2025.101617_bib18","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aba9188","article-title":"MicroRNA-mediated inhibition of transgene expression reduces dorsal root ganglion toxicity by AAV vectors in primates","volume":"12","author":"Hordeaux","year":"2020","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.omtm.2025.101617_bib19","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1016\/j.omtm.2022.01.013","article-title":"Characterization of AAV-mediated dorsal root ganglionopathy","volume":"24","author":"Buss","year":"2022","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.omtm.2025.101617_bib20","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1089\/hum.2021.255","article-title":"Single-Dose Intrathecal Dorsal Root Ganglia Toxicity of Onasemnogene Abeparvovec in Cynomolgus Monkeys","volume":"33","author":"Tukov","year":"2022","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.omtm.2025.101617_bib21","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.ymthe.2024.11.029","article-title":"Dorsal root ganglion toxicity after AAV intra-CSF delivery of a RNAi expression construct into non-human primates and mice","volume":"33","author":"Hawley","year":"2025","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2025.101617_bib22","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1177\/01926233231201408","article-title":"An Overview of Nonclinical and Clinical Liver Toxicity Associated With AAV Gene Therapy","volume":"51","author":"Whiteley","year":"2023","journal-title":"Toxicol. Pathol."},{"key":"10.1016\/j.omtm.2025.101617_bib23","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1177\/01926233241298892","article-title":"Systemic Toxicity of Recombinant Adeno-Associated Virus Gene Therapy Vectors","volume":"52","author":"Assaf","year":"2024","journal-title":"Toxicol. Pathol."},{"key":"10.1016\/j.omtm.2025.101617_bib24","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijcard.2023.131617","article-title":"Gene therapy vector-related myocarditis","volume":"398","author":"Silver","year":"2024","journal-title":"Int. J. Cardiol."},{"key":"10.1016\/j.omtm.2025.101617_bib25","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2022.950651","article-title":"Drug development progress in duchenne muscular dystrophy","volume":"13","author":"Deng","year":"2022","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.omtm.2025.101617_bib26","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1056\/NEJMc2212912","article-title":"Dystrophin Immunity after Gene Therapy for Duchenne's Muscular Dystrophy","volume":"388","author":"Bonnemann","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.omtm.2025.101617_bib27","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1177\/01926233221101309","article-title":"Intrathecal sc-AAV9-CB-GFP: Systemic Distribution Predominates Following Single-Dose Administration in Cynomolgus Macaques","volume":"50","author":"Meseck","year":"2022","journal-title":"Toxicol. Pathol."},{"key":"10.1016\/j.omtm.2025.101617_bib28","first-page":"1438","article-title":"From reads to genes to pathways: differential expression analysis of RNA-Seq experiments using Rsubread and the edgeR quasi-likelihood pipeline","volume":"5","author":"Chen","year":"2016","journal-title":"F1000Res."},{"key":"10.1016\/j.omtm.2025.101617_bib29","doi-asserted-by":"crossref","DOI":"10.1038\/mtm.2014.51","article-title":"Widespread gene transfer in the central nervous system of cynomolgus macaques following delivery of AAV9 into the cisterna magna","volume":"1","author":"Hinderer","year":"2014","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.omtm.2025.101617_bib30","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/labinvest.2012.48","article-title":"The chemokine receptor CXCR3 limits injury after acute toxic liver damage","volume":"92","author":"Zaldivar","year":"2012","journal-title":"Lab. Invest."},{"key":"10.1016\/j.omtm.2025.101617_bib31","doi-asserted-by":"crossref","first-page":"9564","DOI":"10.1128\/JVI.00927-08","article-title":"GammadeltaT cells initiate acute inflammation and injury in adenovirus-infected liver via cytokine-chemokine cross talk","volume":"82","author":"Ajuebor","year":"2008","journal-title":"J. Virol."},{"key":"10.1016\/j.omtm.2025.101617_bib32","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.cytogfr.2011.01.001","article-title":"Regulation of hepatocyte fate by interferon-gamma","volume":"22","author":"Horras","year":"2011","journal-title":"Cytokine Growth Factor Rev."},{"key":"10.1016\/j.omtm.2025.101617_bib33","doi-asserted-by":"crossref","first-page":"389","DOI":"10.3233\/JND-221560","article-title":"Intrathecal Onasemnogene Abeparvovec for Sitting, Nonambulatory Patients with Spinal Muscular Atrophy: Phase I Ascending-Dose Study (STRONG)","volume":"10","author":"Finkel","year":"2023","journal-title":"J. Neuromuscul. Dis."},{"key":"10.1016\/j.omtm.2025.101617_bib34","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/j.neuron.2019.02.017","article-title":"Therapeutic AAV Gene Transfer to the Nervous System: A Clinical Reality","volume":"101","author":"Hudry","year":"2019","journal-title":"Neuron"},{"key":"10.1016\/j.omtm.2025.101617_bib35","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1089\/hum.2017.026","article-title":"Evaluation of Intrathecal Routes of Administration for Adeno-Associated Viral Vectors in Large Animals","volume":"29","author":"Hinderer","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.omtm.2025.101617_bib36","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.jhep.2020.11.001","article-title":"Hepatotoxicity following administration of onasemnogene abeparvovec (AVXS-101) for the treatment of spinal muscular atrophy","volume":"74","author":"Chand","year":"2021","journal-title":"J. Hepatol."}],"container-title":["Molecular Therapy Methods & Clinical Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2329050125002128?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2329050125002128?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T20:30:59Z","timestamp":1776198659000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2329050125002128"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":35,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["S2329050125002128"],"URL":"https:\/\/doi.org\/10.1016\/j.omtm.2025.101617","relation":{},"ISSN":["2329-0501"],"issn-type":[{"value":"2329-0501","type":"print"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Transcriptional changes in non-human primate tissues after intrathecal delivery of serotype 9 adeno-associated viral vector: Insights into organ toxicities","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy Methods & Clinical Development","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.omtm.2025.101617","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy.","name":"copyright","label":"Copyright"}],"article-number":"101617"}}