{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T22:26:29Z","timestamp":1789424789314,"version":"build-2803163510"},"reference-count":36,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:00:00Z","timestamp":1748736000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100022963","name":"Key Research and Development Program of Zhejiang Province","doi-asserted-by":"publisher","award":["2023C03018"],"award-info":[{"award-number":["2023C03018"]}],"id":[{"id":"10.13039\/100022963","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Molecular Therapy Methods &amp; Clinical Development"],"published-print":{"date-parts":[[2025,6]]},"DOI":"10.1016\/j.omtm.2025.101475","type":"journal-article","created":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T19:02:36Z","timestamp":1745002956000},"page":"101475","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"title":["Efficacy and preliminary safety assessment of EXG001-307 AAV gene therapy for spinal muscular atrophy"],"prefix":"10.1016","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2510-0852","authenticated-orcid":false,"given":"Chunjuan","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingzeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peixin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenshu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runyuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongwan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guojie","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1158-2877","authenticated-orcid":false,"given":"Zhenhua","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.omtm.2025.101475_bib1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1101\/sqb.2006.71.001","article-title":"The SMN complex: an assembly machine for RNPs","volume":"71","author":"Battle","year":"2006","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"10.1016\/j.omtm.2025.101475_bib2","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.ceb.2009.02.004","article-title":"The role of RNP biogenesis in spinal muscular atrophy","volume":"21","author":"Chari","year":"2009","journal-title":"Curr. Opin. Cell Biol."},{"key":"10.1016\/j.omtm.2025.101475_bib3","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/nrn2670","article-title":"Spinal muscular atrophy: why do low levels of survival motor neuron protein make motor neurons sick?","volume":"10","author":"Burghes","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.omtm.2025.101475_bib4","doi-asserted-by":"crossref","DOI":"10.3390\/ijms241914873","article-title":"Spinal Muscular Atrophy: An Evolving Scenario through New Perspectives in Diagnosis and Advances in Therapies","volume":"24","author":"Angilletta","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.omtm.2025.101475_bib5","first-page":"88","article-title":"Medical Ethics: Genetic Testing and Spinal Muscular Atrophy","volume":"1","author":"Norrgard","year":"2008","journal-title":"Nat. Educ."},{"key":"10.1016\/j.omtm.2025.101475_bib6","doi-asserted-by":"crossref","DOI":"10.3390\/genes15080999","article-title":"Recent Progress in Gene-Targeting Therapies for Spinal Muscular Atrophy: Promises and Challenges","volume":"15","author":"Haque","year":"2024","journal-title":"Genes"},{"key":"10.1016\/j.omtm.2025.101475_bib7","doi-asserted-by":"crossref","DOI":"10.3390\/genes14071377","article-title":"Spinal Muscular Atrophy Treatment in Patients Identified by Newborn Screening-A Systematic Review","volume":"14","author":"Aragon-Gawinska","year":"2023","journal-title":"Genes"},{"key":"10.1016\/j.omtm.2025.101475_bib8","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2024.1308296","article-title":"The impact of three SMN2 gene copies on clinical characteristics and effect of disease-modifying treatment in patients with spinal muscular atrophy: a systematic literature review","volume":"15","author":"Dosi","year":"2024","journal-title":"Front. Neurol."},{"key":"10.1016\/j.omtm.2025.101475_bib9","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1212\/01.wnl.0000290830.40544.b9","article-title":"The changing natural history of spinal muscular atrophy type 1","volume":"69","author":"Oskoui","year":"2007","journal-title":"Neurology"},{"key":"10.1016\/j.omtm.2025.101475_bib10","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s13023-020-01367-y","article-title":"Natural history of lung function in spinal muscular atrophy","volume":"15","author":"Wijngaarde","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"10.1016\/j.omtm.2025.101475_bib11","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/s41582-020-00413-4","article-title":"Spinal muscular atrophy - insights and challenges in the treatment era","volume":"16","author":"Mercuri","year":"2020","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.omtm.2025.101475_bib12","doi-asserted-by":"crossref","first-page":"3376","DOI":"10.1016\/j.ymthe.2023.11.001","article-title":"The state of cell and gene therapy in 2023","volume":"31","author":"Chancellor","year":"2023","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2025.101475_bib13","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1080\/03007995.2021.1947216","article-title":"Matching-adjusted indirect treatment comparison of onasemnogene abeparvovec and nusinersen for the treatment of symptomatic patients with spinal muscular atrophy type 1","volume":"37","author":"Bischof","year":"2021","journal-title":"Curr. Med. Res. Opin."},{"key":"10.1016\/j.omtm.2025.101475_bib14","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1007\/s12325-019-01088-0","volume":"36","author":"Dabbous","year":"2019","journal-title":"Adv Ther"},{"key":"10.1016\/j.omtm.2025.101475_bib15","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1038\/s44321-024-00037-x","article-title":"Improved gene therapy for spinal muscular atrophy in mice using codon-optimized hSMN1 transgene and hSMN1 gene-derived promotor","volume":"16","author":"Xie","year":"2024","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.omtm.2025.101475_bib16","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41392-024-01780-w","article-title":"Adeno-associated virus as a delivery vector for gene therapy of human diseases","volume":"9","author":"Wang","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.omtm.2025.101475_bib18","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1038\/s41593-021-00827-3","article-title":"Gain of toxic function by long-term AAV9-mediated SMN overexpression in the sensorimotor circuit","volume":"24","author":"Van Alstyne","year":"2021","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.omtm.2025.101475_bib19","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1089\/hum.2018.015","article-title":"Severe Toxicity in Nonhuman Primates and Piglets Following High-Dose Intravenous Administration of an Adeno-Associated Virus Vector Expressing Human SMN","volume":"29","author":"Hinderer","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.omtm.2025.101475_bib20","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."},{"key":"10.1016\/j.omtm.2025.101475_bib21","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1089\/hum.2022.29216.bfs","article-title":"Novartis Confirms Deaths of Two Patients Treated with Gene Therapy Zolgensma","volume":"33","author":"Philippidis","year":"2022","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.omtm.2025.101475_bib22","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.nbd.2011.03.002","article-title":"Characterization of a commonly used mouse model of SMA reveals increased seizure susceptibility and heightened fear response in FVB\/N mice","volume":"43","author":"Gogliotti","year":"2011","journal-title":"Neurobiol. Dis."},{"key":"10.1016\/j.omtm.2025.101475_bib23","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1093\/hmg\/ddi078","article-title":"SMNDelta7, the major product of the centromeric survival motor neuron (SMN2) gene, extends survival in mice with spinal muscular atrophy and associates with full-length SMN","volume":"14","author":"Le","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtm.2025.101475_bib24","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1089\/humc.2013.082","article-title":"Biodistribution of AAV8 vectors expressing human low-density lipoprotein receptor in a mouse model of homozygous familial hypercholesterolemia","volume":"24","author":"Chen","year":"2013","journal-title":"Hum. Gene Ther. Clin. Dev."},{"key":"10.1016\/j.omtm.2025.101475_bib25","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1038\/s41587-023-01974-7","article-title":"Integrated vector genomes may contribute to long-term expression in primate liver after AAV administration","volume":"42","author":"Greig","year":"2024","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.omtm.2025.101475_bib26","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1056\/NEJMoa1706198","article-title":"Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy","volume":"377","author":"Mendell","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.omtm.2025.101475_bib27","doi-asserted-by":"crossref","DOI":"10.1172\/JCI173702","article-title":"Hepatocyte-intrinsic SMN deficiency drives metabolic dysfunction and liver steatosis in spinal muscular atrophy","volume":"134","author":"Leow","year":"2024","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.omtm.2025.101475_bib28","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1007\/s40264-021-01107-6","article-title":"Clinical Trial and Postmarketing Safety of Onasemnogene Abeparvovec Therapy","volume":"44","author":"Day","year":"2021","journal-title":"Drug Saf."},{"key":"10.1016\/j.omtm.2025.101475_bib29","doi-asserted-by":"crossref","DOI":"10.3390\/ph17030394","article-title":"Real-World Safety Data of the Orphan Drug Onasemnogene Abeparvovec (Zolgensma((R))) for the SMA Rare Disease: A Pharmacovigilance Study Based on the EMA Adverse Event Reporting System","volume":"17","author":"Ruggiero","year":"2024","journal-title":"Pharmaceuticals"},{"key":"10.1016\/j.omtm.2025.101475_bib30","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.2025.101475_bib31","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.ymthe.2018.11.013","article-title":"AAV-Mediated Progranulin Delivery to a Mouse Model of Progranulin Deficiency Causes T Cell-Mediated Toxicity","volume":"27","author":"Amado","year":"2019","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2025.101475_bib32","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.omtm.2022.02.002","article-title":"In vivo overexpression of frataxin causes toxicity mediated by iron-sulfur cluster deficiency","volume":"24","author":"Huichalaf","year":"2022","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.omtm.2025.101475_bib33","doi-asserted-by":"crossref","first-page":"6160","DOI":"10.1093\/hmg\/ddv332","article-title":"Low levels of Survival Motor Neuron protein are sufficient for normal muscle function in the SMNDelta7 mouse model of SMA","volume":"24","author":"Iyer","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.omtm.2025.101475_bib34","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s13023-017-0613-5","article-title":"Cardiac pathology in spinal muscular atrophy: a systematic review","volume":"12","author":"Wijngaarde","year":"2017","journal-title":"Orphanet J. Rare Dis."},{"key":"10.1016\/j.omtm.2025.101475_bib35","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1016\/j.ymthe.2020.05.011","article-title":"AAV9-Mediated Expression of SMN Restricted to Neurons Does Not Rescue the Spinal Muscular Atrophy Phenotype in Mice","volume":"28","author":"Besse","year":"2020","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2025.101475_bib36","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1016\/j.bbrc.2011.11.121","article-title":"Direct central nervous system delivery provides enhanced protection following vector mediated gene replacement in a severe model of spinal muscular atrophy","volume":"417","author":"Glascock","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.omtm.2025.101475_bib37","author":"JacksonLaboratory"}],"container-title":["Molecular Therapy Methods &amp; Clinical Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2329050125000701?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2329050125000701?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T18:52:05Z","timestamp":1759863125000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2329050125000701"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":36,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["S2329050125000701"],"URL":"https:\/\/doi.org\/10.1016\/j.omtm.2025.101475","relation":{},"ISSN":["2329-0501"],"issn-type":[{"value":"2329-0501","type":"print"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Efficacy and preliminary safety assessment of EXG001-307 AAV gene therapy for spinal muscular atrophy","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy Methods & Clinical Development","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.omtm.2025.101475","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Author(s). Published by Elsevier Inc. on behalf of The American Society of Gene and Cell Therapy.","name":"copyright","label":"Copyright"}],"article-number":"101475"}}