{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:58:40Z","timestamp":1790629120563,"version":"4.1.0"},"reference-count":48,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,3,1]],"date-time":"2025-03-01T00:00:00Z","timestamp":1740787200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:00:00Z","timestamp":1739318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012165","name":"Key Technologies Research and Development Program","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012165","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":[[2025,3]]},"DOI":"10.1016\/j.omtm.2025.101435","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T00:17:52Z","timestamp":1739492272000},"page":"101435","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":5,"title":["Evaluation of efficacy and safety of AAV8-\u0394C4ATP7B gene therapy in a mutant mouse model of Wilson\u2019s disease"],"prefix":"10.1016","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5954-1803","authenticated-orcid":false,"given":"Chunhua","family":"Zeng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunting","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinshuo","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shehong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kangdi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxian","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zongcai","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingqi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanna","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taolin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueying","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoyong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8956-7238","authenticated-orcid":false,"given":"Wenhao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.omtm.2025.101435_bib1","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/ng1293-327","article-title":"The Wilson disease gene is a putative copper transporting P-type ATPase similar to the Menkes gene","volume":"5","author":"Bull","year":"1993","journal-title":"Nat. Genet."},{"key":"10.1016\/j.omtm.2025.101435_bib2","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/ng1293-338","article-title":"Mapping, cloning and genetic characterization of the region containing the Wilson disease gene","volume":"5","author":"Petrukhin","year":"1993","journal-title":"Nat. Genet."},{"key":"10.1016\/j.omtm.2025.101435_bib3","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1038\/ng1293-344","article-title":"The Wilson disease gene is a copper transporting ATPase with homology to the Menkes disease gene","volume":"5","author":"Tanzi","year":"1993","journal-title":"Nat. Genet."},{"key":"10.1016\/j.omtm.2025.101435_bib4","first-page":"103","article-title":"Biochemical diagnosis of Wilson's disease: an update","volume":"3","author":"Mart\u00ednez-Morillo","year":"2022","journal-title":"Adv. Lab. Med."},{"key":"10.1016\/j.omtm.2025.101435_bib5","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1111\/liv.15319","article-title":"Hepatic ultrastructural features distinguish paediatric Wilson disease from NAFLD and autoimmune hepatitis","volume":"42","author":"Alqahtani","year":"2022","journal-title":"Liver Int."},{"key":"10.1016\/j.omtm.2025.101435_bib6","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/S0140-6736(07)60196-2","article-title":"Wilson's disease","volume":"369","author":"Ala","year":"2007","journal-title":"Lancet"},{"key":"10.1016\/j.omtm.2025.101435_bib7","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1002\/jgh3.12589","article-title":"Long-term outcome of Wilson's disease complicated by liver disease","volume":"5","author":"Arai","year":"2021","journal-title":"JGH Open"},{"key":"10.1016\/j.omtm.2025.101435_bib8","doi-asserted-by":"crossref","DOI":"10.1097\/HC9.0000000000000150","article-title":"Wilson disease: a summary of the updated AASLD Practice Guidance","volume":"7","author":"Alkhouri","year":"2023","journal-title":"Hepatol. Commun."},{"key":"10.1016\/j.omtm.2025.101435_bib9","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/s41572-018-0018-3","article-title":"Wilson disease","volume":"4","author":"Cz\u0142onkowska","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"10.1016\/j.omtm.2025.101435_bib10","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.3390\/cells13141214","article-title":"Navigating the CRISPR\/Cas Landscape for Enhanced Diagnosis and Treatment of Wilson's Disease","volume":"13","author":"Choi","year":"2024","journal-title":"Cell"},{"key":"10.1016\/j.omtm.2025.101435_bib11","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.1177\/1535370221993052","article-title":"A GM1 gangliosidosis mutant mouse model exhibits activated microglia and disturbed autophagy","volume":"246","author":"Liu","year":"2021","journal-title":"Exp. Biol. Med."},{"key":"10.1016\/j.omtm.2025.101435_bib12","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.metabol.2019.02.001","article-title":"A novel GTPCH deficiency mouse model exhibiting tetrahydrobiopterin-related metabolic disturbance and infancy-onset motor impairments","volume":"94","author":"Jiang","year":"2019","journal-title":"Metabolism"},{"key":"10.1016\/j.omtm.2025.101435_bib13","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1002\/hep.32484","article-title":"ATP7B gene therapy of autologous reprogrammed hepatocytes alleviates copper accumulation in a mouse model of Wilson's disease","volume":"76","author":"Cai","year":"2022","journal-title":"Hepatology"},{"key":"10.1016\/j.omtm.2025.101435_bib14","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1002\/hep.28406","article-title":"Activation of liver X receptor\/retinoid X receptor pathway ameliorates liver disease in Atp7B(-\/-) (Wilson disease) mice","volume":"63","author":"Hamilton","year":"2016","journal-title":"Hepatology"},{"key":"10.1016\/j.omtm.2025.101435_bib15","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1111\/jnc.14323","article-title":"Animal models of Wilson disease","volume":"146","author":"Reed","year":"2018","journal-title":"J.\u00a0Neurochem."},{"key":"10.1016\/j.omtm.2025.101435_bib16","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1093\/oxfordjournals.jhered.a110416","article-title":"New mutation causing hereditary hepatitis in the laboratory rat","volume":"78","author":"Yoshida","year":"1987","journal-title":"J.\u00a0Hered."},{"key":"10.1016\/j.omtm.2025.101435_bib17","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0021-9975(08)80268-X","article-title":"The pathology and trace element status of the toxic milk mutant mouse","volume":"110","author":"Howell","year":"1994","journal-title":"J.\u00a0Comp. Pathol."},{"key":"10.1016\/j.omtm.2025.101435_bib18","doi-asserted-by":"crossref","first-page":"423","DOI":"10.2353\/ajpath.2006.050312","article-title":"Consequences of copper accumulation in the livers of the Atp7b-\/- (Wilson disease gene) knockout mice","volume":"168","author":"Huster","year":"2006","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.omtm.2025.101435_bib19","doi-asserted-by":"crossref","first-page":"732","DOI":"10.21037\/atm-20-3090","article-title":"Therapeutic strategies in Wilson disease: pathophysiology and mode of action","volume":"9","author":"Stremmel","year":"2021","journal-title":"Ann. Transl. Med."},{"key":"10.1016\/j.omtm.2025.101435_bib20","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1056\/NEJMra1903585","article-title":"Current and Emerging Issues in Wilson's Disease","volume":"389","author":"Roberts","year":"2023","journal-title":"N.\u00a0Engl. J. Med."},{"key":"10.1016\/j.omtm.2025.101435_bib21","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2022.871877","article-title":"Wilson Disease: Update on Pathophysiology and Treatment","volume":"10","author":"Dev","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"10.1016\/j.omtm.2025.101435_bib22","article-title":"Liver transplantation for late-onset presentations of acute liver failure in Wilson's disease: The UK experience over 2 decades","volume":"2","author":"Shribman","year":"2020","journal-title":"JHEP Rep."},{"key":"10.1016\/j.omtm.2025.101435_bib23","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1002\/hep4.1384","article-title":"Zinc Maintenance Therapy for Wilson Disease: A Comparison Between Zinc Acetate and Alternative Zinc Preparations","volume":"3","author":"Camarata","year":"2019","journal-title":"Hepatol. Commun."},{"key":"10.1016\/j.omtm.2025.101435_bib24","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s13760-022-01872-w","article-title":"Liver transplantation as a treatment for Wilson's disease with neurological presentation: a systematic literature review","volume":"122","author":"Litwin","year":"2022","journal-title":"Acta. Neurol. Belg."},{"key":"10.1016\/j.omtm.2025.101435_bib25","doi-asserted-by":"crossref","first-page":"e2189","DOI":"10.1212\/WNL.0000000000009474","article-title":"Liver transplantation as a rescue therapy for severe neurologic forms of Wilson disease","volume":"94","author":"Poujois","year":"2020","journal-title":"Neurology"},{"key":"10.1016\/j.omtm.2025.101435_bib26","doi-asserted-by":"crossref","DOI":"10.12659\/AOT.930146","article-title":"Diagnostic Dilemma and Treatment Outcome in Acute Liver Failure Due to Wilson's Disease","volume":"26","author":"Stankiewicz","year":"2021","journal-title":"Ann. Transplant."},{"key":"10.1016\/j.omtm.2025.101435_bib27","doi-asserted-by":"crossref","first-page":"21","DOI":"10.21037\/tgh-2020-02","article-title":"Recent advances in Wilson disease","volume":"6","author":"Moini","year":"2021","journal-title":"Transl. Gastroenterol. Hepatol."},{"key":"10.1016\/j.omtm.2025.101435_bib28","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.jhep.2015.09.014","article-title":"Long-term metabolic correction of Wilson's disease in a murine model by gene therapy","volume":"64","author":"Murillo","year":"2016","journal-title":"J.\u00a0Hepatol."},{"key":"10.1016\/j.omtm.2025.101435_bib29","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1002\/hep.30535","article-title":"Liver Expression of a MiniATP7B Gene Results in Long-Term Restoration of Copper Homeostasis in a Wilson Disease Model in Mice","volume":"70","author":"Murillo","year":"2019","journal-title":"Hepatology"},{"key":"10.1016\/j.omtm.2025.101435_bib30","doi-asserted-by":"crossref","first-page":"1494","DOI":"10.1089\/hum.2019.148","article-title":"Long-Term Correction of Copper Metabolism in Wilson's Disease Mice with AAV8 Vector Delivering Truncated ATP7B","volume":"30","author":"Leng","year":"2019","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.omtm.2025.101435_bib31","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1089\/humc.2018.219","article-title":"A Gene Therapy Approach to Improve Copper Metabolism and Prevent Liver Damage in a Mouse Model of Wilson Disease","volume":"30","author":"Greig","year":"2019","journal-title":"Hum. Gene Ther. Clin. Dev."},{"key":"10.1016\/j.omtm.2025.101435_bib32","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.171281","article-title":"Genome editing without nucleases confers proliferative advantage to edited hepatocytes and corrects Wilson disease","volume":"8","author":"Padula","year":"2023","journal-title":"JCI Insight"},{"key":"10.1016\/j.omtm.2025.101435_bib33","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.jhep.2023.10.029","article-title":"Adeno-associated viruses for gene therapy-clinical implications and liver-related complications, a guide for hepatologists","volume":"80","author":"M\u00fccke","year":"2024","journal-title":"J.\u00a0Hepatol."},{"key":"10.1016\/j.omtm.2025.101435_bib34","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.omtm.2022.10.005","article-title":"Edging closer to successful gene therapy for Wilson disease","volume":"27","author":"Sandahl","year":"2022","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.omtm.2025.101435_bib35","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1089\/hum.2022.169","article-title":"Liver Gene Therapy","volume":"33","author":"Nathwani","year":"2022","journal-title":"Hum. Gene Ther."},{"key":"10.1016\/j.omtm.2025.101435_bib36","doi-asserted-by":"crossref","first-page":"G904","DOI":"10.1152\/ajpgi.00262.2005","article-title":"NH2-terminal signals in ATP7B Cu-ATPase mediate its Cu-dependent anterograde traffic in polarized hepatic cells","volume":"289","author":"Guo","year":"2005","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"10.1016\/j.omtm.2025.101435_bib37","article-title":"Novel vectors and approaches for gene therapy in liver diseases","volume":"3","author":"Maestro","year":"2021","journal-title":"JHEP Rep."},{"key":"10.1016\/j.omtm.2025.101435_bib38","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.omtm.2022.08.004","article-title":"Full-length ATP7B reconstituted through protein trans-splicing corrects Wilson disease in mice","volume":"26","author":"Padula","year":"2022","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"10.1016\/j.omtm.2025.101435_bib39","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s40259-023-00585-7","article-title":"Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer","volume":"37","author":"Arjomandnejad","year":"2023","journal-title":"BioDrugs"},{"key":"10.1016\/j.omtm.2025.101435_bib40","doi-asserted-by":"crossref","first-page":"3123","DOI":"10.1016\/j.ymthe.2023.10.015","article-title":"Lethal immunotoxicity in high-dose systemic AAV therapy","volume":"31","author":"Duan","year":"2023","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2025.101435_bib41","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1016\/j.ymthe.2017.03.013","article-title":"Lipid Nanoparticle Systems for Enabling Gene Therapies","volume":"25","author":"Cullis","year":"2017","journal-title":"Mol. Ther."},{"key":"10.1016\/j.omtm.2025.101435_bib42","doi-asserted-by":"crossref","DOI":"10.1016\/j.omtn.2023.102050","article-title":"In\u00a0vivo genome editing using 244-cis LNPs and low-dose AAV achieves therapeutic threshold in hemophilia A mice","volume":"34","author":"Han","year":"2023","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"10.1016\/j.omtm.2025.101435_bib43","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/cge.12951","article-title":"Spectrum of ATP7B mutations and genotype-phenotype correlation in large-scale Chinese patients with Wilson Disease","volume":"92","author":"Cheng","year":"2017","journal-title":"Clin. Genet."},{"key":"10.1016\/j.omtm.2025.101435_bib44","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s12876-022-02186-0","article-title":"Assessment of the diagnostic value of serum ceruloplasmin for Wilson's disease in children","volume":"22","author":"Lu","year":"2022","journal-title":"BMC Gastroenterol."},{"key":"10.1016\/j.omtm.2025.101435_bib45","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1002\/ajmg.a.61254","article-title":"Clinical features and mutational analysis in 114 young children with Wilson disease from South China","volume":"179","author":"Li","year":"2019","journal-title":"Am. J. Med. Genet."},{"key":"10.1016\/j.omtm.2025.101435_bib46","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1039\/C9MT00148D","article-title":"Obesity is associated with copper elevation in serum and tissues","volume":"11","author":"Yang","year":"2019","journal-title":"Metallomics"},{"key":"10.1016\/j.omtm.2025.101435_bib47","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1055\/s-0031-1286055","article-title":"Pathology of the liver in copper overload","volume":"31","author":"Johncilla","year":"2011","journal-title":"Semin. Liver Dis."},{"key":"10.1016\/j.omtm.2025.101435_bib48","first-page":"542","article-title":"Effect of Copper Staining in Wilson Disease: A Liver Explant Study","volume":"15","author":"Karadag","year":"2017","journal-title":"Exp. Clin. Transplant."}],"container-title":["Molecular Therapy Methods &amp; Clinical Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2329050125000300?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2329050125000300?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:59:05Z","timestamp":1742518745000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2329050125000300"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["S2329050125000300"],"URL":"https:\/\/doi.org\/10.1016\/j.omtm.2025.101435","relation":{},"ISSN":["2329-0501"],"issn-type":[{"value":"2329-0501","type":"print"}],"subject":[],"published":{"date-parts":[[2025,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Evaluation of efficacy and safety of AAV8-\u0394C4ATP7B gene therapy in a mutant mouse model of Wilson\u2019s disease","name":"articletitle","label":"Article Title"},{"value":"Molecular Therapy Methods & Clinical Development","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.omtm.2025.101435","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":"101435"}}