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Adv."],"published-print":{"date-parts":[[2026,5,29]]},"abstract":"<jats:p>\n                    A major challenge in hepatitis C virus (HCV) research is the lack of an in vivo model that supports robust infection, antiviral testing, and vaccine development. The humanized liver chimeric mouse models support high-level viremia from various HCV sources, although they lack an immune system. Here, we used\n                    <jats:italic toggle=\"yes\">\n                      Fah\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      \/Rag2\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                      \/Il2rg\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    (FRG) and urokinase-type plasminogen activator\u2013severe combined immunodeficiency (\n                    <jats:italic toggle=\"yes\">uPA<\/jats:italic>\n                    -SCID) mice engrafted with primary human hepatocytes to investigate HCV infection dynamics and evaluate lipid nanoparticle (LNP)\u2013mediated delivery of full-length HCV RNA. Mice were inoculated with HCV-positive chimpanzee serum or LNP-encapsulated HCV RNA of various genotypes and developed viremia reaching 10\n                    <jats:sup>8<\/jats:sup>\n                    copies per milliliter. RNA-LNP\u2013mediated infection mirrored serum-derived infection that was transmissible to na\u00efve mice. Glecaprevir\/pibrentasvir cleared viremia, and treated mice could be reinfected. The proportion of antibody-free HCV RNA in human serum correlated with infectivity. These findings demonstrate the utility of this model for studying HCV infection and treatment and highlight LNP-based RNA delivery as a scalable approach for generating standardized challenge inocula.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aef1160","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T18:00:46Z","timestamp":1780077646000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Hepatitis C virus infection dynamics, treatment, and lipid nanoparticle\u2013mediated infection in humanized liver chimeric mouse models"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2834-9071","authenticated-orcid":true,"given":"Seung Bum","family":"Park","sequence":"first","affiliation":[{"name":"Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"S\u00e1nchez-Meza","sequence":"additional","affiliation":[{"name":"Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3842-3942","authenticated-orcid":true,"given":"Regina","family":"Umarova","sequence":"additional","affiliation":[{"name":"Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4701-4576","authenticated-orcid":true,"given":"Justin","family":"Shields","sequence":"additional","affiliation":[{"name":"Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5805-4859","authenticated-orcid":true,"given":"Laura","family":"Collignon","sequence":"additional","affiliation":[{"name":"Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xhuliana","family":"Sula","sequence":"additional","affiliation":[{"name":"Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4472-3257","authenticated-orcid":true,"given":"Kenn","family":"Holmbeck","sequence":"additional","affiliation":[{"name":"Copenhagen Hepatitis C Program (CO-HEP), Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre and Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0824-6131","authenticated-orcid":true,"given":"Ji Hoon","family":"Oh","sequence":"additional","affiliation":[{"name":"Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Farci","sequence":"additional","affiliation":[{"name":"Hepatic Pathogenesis Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Bethesda, MD 20892, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0983-7267","authenticated-orcid":true,"given":"D. 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