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Therefore, it is necessary to explore new therapeutic approaches and combined therapy strategies. Anticodon engineered transfer RNA (ACE\u2010tRNA) has been widely applied in the treatment of genetic diseases caused by nonsense mutations. However, its role in antiviral therapy has not been reported yet. In this study, ACE\u2010tRNAs are designed to target the highly conserved stop codon (UAG) of HBV core protein (HBc). All designed ACE\u2010tRNAs can read through the stop codon of HBc. Among them, tRNA\n                    <jats:sup>SUAG<\/jats:sup>\n                    might promote HBc phosphorylation by introducing a phosphorylatable serine into the C\u2010terminal domain of HBc, thereby potentially reducing HBc levels and inhibiting HBV replication by promoting the degradation of HBc through the ubiquitin\u2010proteasome pathway. In addition, ACE\u2010tRNA and CRISPR\/Cas9 technologies can be effectively integrated through a tRNA\n                    <jats:sup>SUAG<\/jats:sup>\n                    \u2010gRNA tandem array and achieve the combined inhibition of HBV replication. This study innovatively applied ACE\u2010tRNA to promote HBc degradation by introducing an amino acid that may be post\u2010translationally modified and subsequently inhibit HBV replication. In addition, this study presents a promising therapeutic strategy for promoting the clearance of HBV infection by integrating ACE\u2010tRNA and CRISPR\/Cas9 technology.\n                  <\/jats:p>","DOI":"10.1002\/advs.202503534","type":"journal-article","created":{"date-parts":[[2025,9,13]],"date-time":"2025-09-13T02:51:22Z","timestamp":1757731882000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Anticodon Engineered Transfer RNA (tRNA\n                    <sup>SUAG<\/sup>\n                    ) Inhibits Hepatitis B Virus Replication by Promoting the Degradation of Core Protein"],"prefix":"10.1002","volume":"12","author":[{"given":"Xingwen","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Microbiology &amp; Infectious Disease Center School of Basic Medical Sciences Peking University Health Science Center  38 Xueyuan Road, Haidian District Beijing 100191 China"},{"name":"NHC Key Laboratory of Medical Immunology Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiying","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Infectious Disease Center School of Basic Medical Sciences Peking University Health Science Center  38 Xueyuan Road, Haidian District Beijing 100191 China"},{"name":"NHC Key Laboratory of Medical Immunology Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziheng","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Infectious Disease Center School of Basic Medical Sciences Peking University Health Science Center  38 Xueyuan Road, Haidian District Beijing 100191 China"},{"name":"NHC Key Laboratory of Medical Immunology Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Infectious Disease Center School of Basic Medical Sciences Peking University Health Science Center  38 Xueyuan Road, Haidian District Beijing 100191 China"},{"name":"NHC Key Laboratory of Medical Immunology Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yarong","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Infectious Disease Center School of Basic Medical Sciences Peking University Health Science Center  38 Xueyuan Road, Haidian District Beijing 100191 China"},{"name":"NHC Key Laboratory of Medical Immunology Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Infectious Disease Center School of Basic Medical Sciences Peking University Health Science Center  38 Xueyuan Road, Haidian District Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Infectious Disease Center School of Basic Medical Sciences Peking University Health Science Center  38 Xueyuan Road, Haidian District Beijing 100191 China"},{"name":"NHC Key Laboratory of Medical Immunology Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6518-948X","authenticated-orcid":false,"given":"Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Infectious Disease Center School of Basic Medical Sciences Peking University Health Science Center  38 Xueyuan Road, Haidian District Beijing 100191 China"},{"name":"NHC Key Laboratory of Medical Immunology Peking University  Beijing 100191 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,12]]},"reference":[{"key":"e_1_2_9_1_1","unstructured":"World Health Organization Global hepatitis report 2024: action for access in low\u2010 and middle\u2010income countries.Geneva: World Health Organization 2024 (https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/hepatitis\u2010b accessed: June2024)."},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.11.003"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29800"},{"key":"e_1_2_9_4_1","first-page":"1425","volume":"11","author":"You H.","year":"2023","journal-title":"J. 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