{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:17:52Z","timestamp":1792642672528,"version":"4.5.0"},"reference-count":43,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T00:00:00Z","timestamp":1753920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>In a previous study, eight chronically HBV-infected nucleos (t)ide analog (NA)-na\u00efve patients began receiving entecavir (ETV) concomitant with a single ARC-520 HBV siRNA injection. This single dose of ARC-520 (SD) was followed by 6\u20138 months of ETV alone before the patients received 4\u20139 monthly doses of ARC-520, the multi-dose (MD) period, while continuing ETV. Quantities of HBV DNA, RNA, and antigens were measured from serum and a liver biopsy collected ~30 months after the last MD from five patients. All full-length HBV transcripts from the livers were characterized. Viral parameters and HBV transcripts from patients were compared to these measurements collected at multiple points in ARC-520 + ETV-treated chronically HBV-infected chimpanzees. Multiple forms of HBx mRNA were observed, and these differed between chimpanzees and patients. Products of cccDNA were greatly decreased in patients who were previously highly viremic and HBeAg+, although a biopsied patient had similar amounts of cccDNA to the highly viremic HBeAg+ chimpanzees. The comparison of all HBV transcripts and cccDNA levels between patients and chimpanzees demonstrate the transcriptional silencing of cccDNA following the siRNA treatment of patients but not the chimpanzees that received a different treatment regimen. Results from this small study suggest that continued NA treatment during and between periods of HBV antigen re-expression post-siRNA treatment enhanced viral parameter reductions.<\/jats:p>","DOI":"10.3390\/microorganisms13081787","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T06:37:47Z","timestamp":1754030267000},"page":"1787","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Virological Insights from ARC-520 siRNA and Entecavir Treated Chronically HBV-Infected Patients and Chimpanzees"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8203-7493","authenticated-orcid":false,"given":"Christine I.","family":"Wooddell","sequence":"first","affiliation":[{"name":"Arrowhead Pharmaceuticals Inc., 502 S. Rosa Road, Madison, WI 53719, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2266-3935","authenticated-orcid":false,"given":"Lung Yi","family":"Mak","sequence":"additional","affiliation":[{"name":"Department of Medicine, State Key Laboratory of Liver Research, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai-Kay","family":"Seto","sequence":"additional","affiliation":[{"name":"Department of Medicine, State Key Laboratory of Liver Research, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce D.","family":"Given","sequence":"additional","affiliation":[{"name":"Arrowhead Pharmaceuticals Inc., 177 E. Colorado Boulevard, Suite 700, Pasadena, CA 91105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7985-7725","authenticated-orcid":false,"given":"Man-Fung","family":"Yuen","sequence":"additional","affiliation":[{"name":"Department of Medicine, State Key Laboratory of Liver Research, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1016\/S2468-1253(23)00197-8","article-title":"Global prevalence, cascade of care, and prophylaxis coverage of hepatitis B in 2022: A modelling study","volume":"8","year":"2023","journal-title":"Lancet Gastroenterol. 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