{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:59:29Z","timestamp":1791082769914,"version":"4.1.0"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T00:00:00Z","timestamp":1740096000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Virus Research"],"published-print":{"date-parts":[[2025,4]]},"DOI":"10.1016\/j.virusres.2025.199550","type":"journal-article","created":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T00:53:53Z","timestamp":1740185633000},"page":"199550","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":7,"special_numbering":"C","title":["Adeno-associated virus 2 CRISPR\/Cas9-mediated targeting of hepatitis B virus in tree shrews"],"prefix":"10.1016","volume":"354","author":[{"given":"Md Haroon Or","family":"Rashid","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Enamul Hoque","family":"Kayesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Abul","family":"Hashem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Hifumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shintaro","family":"Ogawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriaki","family":"Miyoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhito","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michinori","family":"Kohara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4403-2018","authenticated-orcid":false,"given":"Kyoko","family":"Tsukiyama-Kohara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"Pt 8","key":"10.1016\/j.virusres.2025.199550_bib0001","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1099\/0022-1317-83-8-2059","article-title":"Genotype H: a new Amerindian genotype of hepatitis B virus revealed in Central America","volume":"83","author":"Arauz-Ruiz","year":"2002","journal-title":"J. Gen. Virol."},{"issue":"1","key":"10.1016\/j.virusres.2025.199550_bib0002","doi-asserted-by":"crossref","DOI":"10.3390\/ijms25010334","article-title":"CRISPR\/Cas9 as a new antiviral strategy for treating Hepatitis viral infections","volume":"25","author":"Bartosh","year":"2023","journal-title":"Int. J. Mol. Sci."},{"issue":"7","key":"10.1016\/j.virusres.2025.199550_bib0003","article-title":"A recent prevalence of Hepatitis B virus (HBV) genotypes and subtypes in Asia: a systematic review and meta-analysis","volume":"11","author":"Bello","year":"2023","journal-title":"Healthc. (Basel)"},{"issue":"5","key":"10.1016\/j.virusres.2025.199550_bib0004","doi-asserted-by":"crossref","first-page":"e866","DOI":"10.1002\/iid3.866","article-title":"CRISPR\/Cas9 for hepatitis B virus infection treatment","volume":"11","author":"Cai","year":"2023","journal-title":"Immun. Inflamm. Dis."},{"issue":"5291","key":"10.1016\/j.virusres.2025.199550_bib0005","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1126\/science.274.5291.1379","article-title":"Liver failure and defective hepatocyte regeneration in interleukin-6-deficient mice","volume":"274","author":"Cressman","year":"1996","journal-title":"Science"},{"issue":"6","key":"10.1016\/j.virusres.2025.199550_bib0006","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1053\/j.gastro.2011.12.061","article-title":"Epidemiology of viral hepatitis and hepatocellular carcinoma","volume":"142","author":"El-Serag","year":"2012","journal-title":"Gastroenterology"},{"issue":"6","key":"10.1016\/j.virusres.2025.199550_bib0007","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/j.ebiom.2015.04.007","article-title":"Serum DHCR24 auto-antibody as a new biomarker for progression of Hepatitis C","volume":"2","author":"Ezzikouri","year":"2015","journal-title":"EBioMedicine"},{"issue":"1","key":"10.1016\/j.virusres.2025.199550_bib0008","doi-asserted-by":"crossref","DOI":"10.1172\/JCI134529","article-title":"TLR3 controls constitutive IFN-beta antiviral immunity in human fibroblasts and cortical neurons","volume":"131","author":"Gao","year":"2021","journal-title":"J. Clin. Invest."},{"issue":"1","key":"10.1016\/j.virusres.2025.199550_bib0009","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/hep.30111","article-title":"An association between core mutations in Hepatitis B Virus genotype F1b and hepatocellular carcinoma in Alaskan native people","volume":"69","author":"Hayashi","year":"2019","journal-title":"Hepatology"},{"issue":"2","key":"10.1016\/j.virusres.2025.199550_bib0010","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.jhep.2021.02.017","article-title":"Clinical efficacy of a novel, high-sensitivity HBcrAg assay in the management of chronic hepatitis B and HBV reactivation","volume":"75","author":"Inoue","year":"2021","journal-title":"J. Hepatol."},{"issue":"1","key":"10.1016\/j.virusres.2025.199550_bib0011","doi-asserted-by":"crossref","first-page":"230","DOI":"10.4049\/jimmunol.1701216","article-title":"Innate recognition of the microbiota by TLR1 promotes epithelial homeostasis and prevents chronic inflammation","volume":"201","author":"Kamdar","year":"2018","journal-title":"J. Immunol."},{"key":"10.1016\/j.virusres.2025.199550_bib0012","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s12876-015-0283-5","article-title":"IL-6, through p-STAT3 rather than p-STAT1, activates hepatocarcinogenesis and affects survival of hepatocellular carcinoma patients: a cohort study","volume":"15","author":"Kao","year":"2015","journal-title":"BMC Gastroenterol."},{"issue":"6","key":"10.1016\/j.virusres.2025.199550_bib0013","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1111\/j.1478-3231.2011.02742.x","article-title":"Rather than interleukin-27, interleukin-6 expresses positive correlation with liver severity in naive hepatitis B infection patients","volume":"32","author":"Kao","year":"2012","journal-title":"Liver Int."},{"key":"10.1016\/j.virusres.2025.199550_bib0014","doi-asserted-by":"crossref","DOI":"10.1016\/j.virusres.2020.198191","article-title":"Development of an in vivo delivery system for CRISPR\/Cas9-mediated targeting of hepatitis B virus cccDNA","volume":"290","author":"Kayesh","year":"2020","journal-title":"Virus Res."},{"key":"10.1016\/j.virusres.2025.199550_bib0015","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.virusres.2017.05.013","article-title":"Interferon-beta response is impaired by hepatitis B virus infection in Tupaia belangeri","volume":"237","author":"Kayesh","year":"2017","journal-title":"Virus Res."},{"key":"10.1016\/j.virusres.2025.199550_bib0016","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.meegid.2017.04.003","article-title":"Susceptibility and initial immune response of Tupaia belangeri cells to dengue virus infection","volume":"51","author":"Kayesh","year":"2017","journal-title":"Infect. Genet. Evolut."},{"key":"10.1016\/j.virusres.2025.199550_bib0017","doi-asserted-by":"crossref","DOI":"10.3389\/fmicb.2023.1249718","article-title":"TLR agonists as vaccine adjuvants in the prevention of viral infections: an overview","volume":"14","author":"Kayesh","year":"2023","journal-title":"Front. Microbiol."},{"issue":"8","key":"10.1016\/j.virusres.2025.199550_bib0018","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.4254\/wjh.v7.i8.1030","article-title":"Current and future antiviral drug therapies of hepatitis B chronic infection","volume":"7","author":"Koumbi","year":"2015","journal-title":"World J. Hepatol."},{"key":"10.1016\/j.virusres.2025.199550_bib0019","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.3389\/fimmu.2018.02080","article-title":"Inhibition of HBV expression in HBV transgenic mice using AAV-delivered CRISPR-SaCas9","volume":"9","author":"Li","year":"2018","journal-title":"Front. Immunol."},{"key":"10.1016\/j.virusres.2025.199550_bib0020","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3389\/fcimb.2017.00091","article-title":"Removal of integrated Hepatitis B virus DNA using CRISPR-Cas9","volume":"7","author":"Li","year":"2017","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"10.1016\/j.virusres.2025.199550_bib0021","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-981-13-9151-4_1","article-title":"Hepatitis B virus infection: overview","volume":"1179","author":"Li","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"issue":"6","key":"10.1016\/j.virusres.2025.199550_bib0022","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1292\/jvms.21-0026","article-title":"A systematic study of Tupaia as a model for human acute hepatitis B infection","volume":"83","author":"Li","year":"2021","journal-title":"J. Vet. Med. Sci."},{"issue":"8","key":"10.1016\/j.virusres.2025.199550_bib0023","doi-asserted-by":"crossref","first-page":"2252","DOI":"10.1099\/vir.0.000159","article-title":"Inhibition of hepatitis B virus by the CRISPR\/Cas9 system via targeting the conserved regions of the viral genome","volume":"96","author":"Liu","year":"2015","journal-title":"J. Gen. Virol."},{"issue":"3 Pt B","key":"10.1016\/j.virusres.2025.199550_bib0024","doi-asserted-by":"crossref","first-page":"485","DOI":"10.3851\/IMP2604","article-title":"HBV genotype F: natural history and treatment","volume":"18","author":"Marciano","year":"2013","journal-title":"Antivir. Ther. (Lond.)"},{"issue":"4","key":"10.1016\/j.virusres.2025.199550_bib0025","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1016\/j.jhep.2021.04.051","article-title":"Ubiquitous expression of HBsAg from integrated HBV DNA in patients with low viral load","volume":"75","author":"Meier","year":"2021","journal-title":"J. Hepatol."},{"issue":"8","key":"10.1016\/j.virusres.2025.199550_bib0026","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1038\/90968","article-title":"Hepatitis C virus replication in mice with chimeric human livers","volume":"7","author":"Mercer","year":"2001","journal-title":"Nat. Med."},{"issue":"3","key":"10.1016\/j.virusres.2025.199550_bib0027","doi-asserted-by":"crossref","first-page":"e59611","DOI":"10.1371\/journal.pone.0059611","article-title":"Targeted induction of interferon-lambda in humanized chimeric mouse liver abrogates hepatotropic virus infection","volume":"8","author":"Nakagawa","year":"2013","journal-title":"PLoS One"},{"issue":"Pt 10","key":"10.1016\/j.virusres.2025.199550_bib0028","doi-asserted-by":"crossref","first-page":"2575","DOI":"10.1099\/0022-1317-69-10-2575","article-title":"Typing hepatitis B virus by homology in nucleotide sequence: comparison of surface antigen subtypes","volume":"69","author":"Okamoto","year":"1988","journal-title":"J. Gen. Virol."},{"issue":"39","key":"10.1016\/j.virusres.2025.199550_bib0029","doi-asserted-by":"crossref","first-page":"3931","DOI":"10.18632\/oncotarget.27002","article-title":"Free episomal and integrated HBV DNA in HBsAg-negative patients with intrahepatic cholangiocarcinoma","volume":"10","author":"Pollicino","year":"2019","journal-title":"Oncotarget."},{"issue":"7","key":"10.1016\/j.virusres.2025.199550_bib0030","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1136\/gutjnl-2023-330414","article-title":"HBV integrations reshaping genomic structures promote hepatocellular carcinoma","volume":"73","author":"Qian","year":"2024","journal-title":"Gut"},{"issue":"1","key":"10.1016\/j.virusres.2025.199550_bib0031","doi-asserted-by":"crossref","first-page":"12372","DOI":"10.1038\/s41598-019-48867-x","article-title":"Construction of complete Tupaia belangeri transcriptome database by whole-genome and comprehensive RNA sequencing","volume":"9","author":"Sanada","year":"2019","journal-title":"Sci. Rep."},{"issue":"2","key":"10.1016\/j.virusres.2025.199550_bib0032","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.bbrc.2015.11.121","article-title":"Property of hepatitis B virus replication in Tupaia belangeri hepatocytes","volume":"469","author":"Sanada","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"11","key":"10.1016\/j.virusres.2025.199550_bib0033","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1038\/sj.mt.6300293","article-title":"Characterization of the relationship of AAV capsid domain swapping to liver transduction efficiency","volume":"15","author":"Shen","year":"2007","journal-title":"Mol. Ther."},{"issue":"11","key":"10.1016\/j.virusres.2025.199550_bib0034","doi-asserted-by":"crossref","first-page":"3484","DOI":"10.1128\/JCM.00726-13","article-title":"Application of a newly developed high-sensitivity HBsAg chemiluminescent enzyme immunoassay for hepatitis B patients with HBsAg seroclearance","volume":"51","author":"Shinkai","year":"2013","journal-title":"J. Clin. Microbiol."},{"issue":"4","key":"10.1016\/j.virusres.2025.199550_bib0035","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1538\/expanim.63.367","article-title":"Tupaia belangeri as an experimental animal model for viral infection","volume":"63","author":"Tsukiyama-Kohara","year":"2014","journal-title":"Experim. Anim."},{"issue":"5","key":"10.1016\/j.virusres.2025.199550_bib0036","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1002\/hep.30054","article-title":"Hepatitis B virus evasion from cyclic guanosine monophosphate-adenosine monophosphate synthase sensing in Human hepatocytes","volume":"68","author":"Verrier","year":"2018","journal-title":"Hepatology"},{"issue":"3","key":"10.1016\/j.virusres.2025.199550_bib0037","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1534\/g3.114.015834","article-title":"Comparison of T7E1 and surveyor mismatch cleavage assays to detect mutations triggered by engineered nucleases","volume":"5","author":"Vouillot","year":"2015","journal-title":"G3 (Bethesda)"},{"issue":"1","key":"10.1016\/j.virusres.2025.199550_bib0038","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/hep.510240101","article-title":"Hepatitis B virus infection of tupaia hepatocytes in vitro and in vivo","volume":"24","author":"Walter","year":"1996","journal-title":"Hepatology"},{"issue":"7","key":"10.1016\/j.virusres.2025.199550_bib0039","doi-asserted-by":"crossref","first-page":"1142","DOI":"10.1136\/gutjnl-2023-330788","article-title":"Pancreas-directed AAV8-hSPINK1 gene therapy safely and effectively protects against pancreatitis in mice","volume":"73","author":"Wang","year":"2024","journal-title":"Gut"},{"issue":"105","key":"10.1016\/j.virusres.2025.199550_bib0040","first-page":"255","article-title":"The CRISPR\/Cas9 genome editing methodology as a weapon against human viruses","volume":"19","author":"White","year":"2015","journal-title":"Discov. Med."},{"key":"10.1016\/j.virusres.2025.199550_bib0041","doi-asserted-by":"crossref","first-page":"e00049","DOI":"10.7554\/eLife.00049","article-title":"Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus","volume":"1","author":"Yan","year":"2012","journal-title":"eLife"},{"key":"10.1016\/j.virusres.2025.199550_bib0042","doi-asserted-by":"crossref","DOI":"10.3389\/fmicb.2021.665184","article-title":"Inhibition of Hepatitis B Virus by AAV8-derived CRISPR\/SaCas9 expressed from liver-specific promoters","volume":"12","author":"Yan","year":"2021","journal-title":"Front. Microbiol."},{"issue":"1","key":"10.1016\/j.virusres.2025.199550_bib0043","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1053\/j.gastro.2022.10.008","article-title":"Current best practice in Hepatitis B management and understanding long-term prospects for cure","volume":"164","author":"Yardeni","year":"2023","journal-title":"Gastroenterology"},{"key":"10.1016\/j.virusres.2025.199550_bib0044","doi-asserted-by":"crossref","first-page":"18035","DOI":"10.1038\/nrdp.2018.35","article-title":"Hepatitis B virus infection","volume":"4","author":"Yuen","year":"2018","journal-title":"Nat. Rev. Dis. Primer."},{"key":"10.1016\/j.virusres.2025.199550_bib0045","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1186\/s12879-014-0608-y","article-title":"A novel method for detection of HBVcccDNA in hepatocytes using rolling circle amplification combined with in situ PCR","volume":"14","author":"Zhong","year":"2014","journal-title":"BMC. Infect. Dis."}],"container-title":["Virus Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168170225000267?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168170225000267?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T09:59:33Z","timestamp":1741859973000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168170225000267"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4]]},"references-count":45,"alternative-id":["S0168170225000267"],"URL":"https:\/\/doi.org\/10.1016\/j.virusres.2025.199550","relation":{},"ISSN":["0168-1702"],"issn-type":[{"value":"0168-1702","type":"print"}],"subject":[],"published":{"date-parts":[[2025,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Adeno-associated virus 2 CRISPR\/Cas9-mediated targeting of hepatitis B virus in tree shrews","name":"articletitle","label":"Article Title"},{"value":"Virus Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.virusres.2025.199550","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 B.V.","name":"copyright","label":"Copyright"}],"article-number":"199550"}}