{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:48:43Z","timestamp":1788929323933,"version":"build-2803163510"},"reference-count":127,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Hepatitis B and C viruses (HBV and HCV) remain among the leading causes of liver disease worldwide. Current antiviral drugs, such as nucleotide analogues (NAs), can reduce the replication of new HBV and HCV infections but cannot completely eliminate chronic infections. This is primarily because a stable form of viral DNA, known as covalently closed circular DNA (cccDNA), persists in liver cells and continues to sustain the infection. In recent years, the CRISPR\/Cas9 gene\u2010editing system has emerged as a powerful tool for precisely cutting and inactivating specific DNA sequences. Due to its efficiency and ease of use, researchers have applied CRISPR\/Cas9 in numerous studies to directly target and disrupt the HBV genome, demonstrating promising antiviral effects in both cell cultures and animal models. Targeting multiple sites within the HBV genome has been shown to further enhance its effectiveness, paving the way for potential combination therapies aimed at disabling both cccDNA and HBV and HCV DNA integrated into the host genome. Despite its potential, CRISPR\/Cas9 still faces significant challenges before clinical application, most notably the risk of off\u2010target effects\u2014unintended cleavage of non\u2010target DNA sequences\u2014and the difficulty of delivering the system efficiently into liver cells in\u00a0vivo. Future progress will depend on improving the tool's precision, efficiency, flexibility and delivery methods. In this review, we explore recent advances in designing guide RNAs (gRNAs) for targeting HBV and HCV, as well as the delivery systems used to transport CRISPR\/Cas9 into cells. We also discuss the remaining challenges and potential strategies for advancing CRISPR\/Cas9 from the laboratory toward a viable clinical cure for HBV and HCV.<\/jats:p>","DOI":"10.1111\/jcmm.70986","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T10:42:16Z","timestamp":1767868936000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Disrupting Viral Persistence:\n                    <scp>CRISPR<\/scp>\n                    \/Cas9\u2010Based Strategies for Hepatitis B and C Treatment, and Challenges"],"prefix":"10.1111","volume":"30","author":[{"given":"Meng\u2010Fan","family":"Li","sequence":"first","affiliation":[{"name":"Food Science School Guangdong Pharmaceutical University  Zhongshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akmal","family":"Zubair","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Quaid\u2010i\u2010Azam University  Islamabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0201-8880","authenticated-orcid":false,"given":"Safa","family":"Wdidi","sequence":"additional","affiliation":[{"name":"Faculty of Medical Sciences Laboratory, Oncology Research Center University of Shendi  Shendi Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2698-0786","authenticated-orcid":false,"given":"Shan","family":"He","sequence":"additional","affiliation":[{"name":"Faculty of Science, Technology and Engineering Charles Darwin University  Casuarina Northwest Territories Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"issue":"4","key":"e_1_2_18_2_1","doi-asserted-by":"crossref","DOI":"10.3390\/cells11040741","article-title":"Hepatitis B Viral Protein HBx and the Molecular Mechanisms Modulating the Hallmarks of Hepatocellular Carcinoma: A Comprehensive Review","volume":"11","author":"Sivasudhan E.","year":"2022","journal-title":"Cells"},{"issue":"24","key":"e_1_2_18_3_1","doi-asserted-by":"crossref","DOI":"10.3390\/ijms222413578","article-title":"Pathogenesis of Autoimmune Hepatitis\u2010Cellular and Molecular Mechanisms","volume":"22","author":"Sirbe C.","year":"2021","journal-title":"International Journal of Molecular Sciences"},{"issue":"8","key":"e_1_2_18_4_1","doi-asserted-by":"crossref","DOI":"10.3390\/v13081463","article-title":"Mechanism of Hepatitis B Virus cccDNA Formation","volume":"13","author":"Wei L.","year":"2021","journal-title":"Viruses"},{"key":"e_1_2_18_5_1","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1016\/j.csbj.2021.03.038","article-title":"Structural and Molecular Biology of Hepatitis E Virus","volume":"19","author":"Wang B.","year":"2021","journal-title":"Computational and Structural Biotechnology Journal"},{"key":"e_1_2_18_6_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.60095"},{"issue":"4","key":"e_1_2_18_7_1","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.jhep.2021.05.041","article-title":"Loss of Hepatocyte Identity Following Aberrant YAP Activation: A Key Mechanism in Alcoholic Hepatitis","volume":"75","author":"Bou Saleh M.","year":"2021","journal-title":"Journal of Hepatology"},{"issue":"1","key":"e_1_2_18_8_1","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1038\/s41467-021-21850-9","article-title":"Hepatitis B Virus cccDNA Is Formed Through Distinct Repair Processes of Each Strand","volume":"12","author":"Wei L.","year":"2021","journal-title":"Nature Communications"},{"issue":"13","key":"e_1_2_18_9_1","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.3748\/wjg.v27.i13.1267","article-title":"Metabolic Complications of Hepatitis C Virus Infection","volume":"27","author":"Chaudhari R.","year":"2021","journal-title":"World Journal of Gastroenterology"},{"key":"e_1_2_18_10_1","first-page":"5","article-title":"Hepatitis B Virus\u2010Associated Hepatocellular Carcinoma","volume":"14","author":"Rizzo G. 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Evidence Indicates Endogenous Exosomes Can Deliver Functional gRNA and Cas9 Protein","volume":"15","author":"Chen R.","year":"2019","journal-title":"Small"},{"issue":"9","key":"e_1_2_18_78_1","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1007\/s00018-019-03021-8","article-title":"Orthologous CRISPR\/Cas9 Systems for Specific and Efficient Degradation of Covalently Closed Circular DNA of Hepatitis B Virus","volume":"76","author":"Kostyushev D.","year":"2019","journal-title":"Cellular and Molecular Life Sciences"},{"issue":"8","key":"e_1_2_18_79_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1007874","article-title":"Human Apolipoprotein E Promotes Hepatitis B Virus Infection and Production","volume":"15","author":"Qiao L.","year":"2019","journal-title":"PLoS Pathogens"},{"key":"e_1_2_18_80_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.omtn.2018.01.002","article-title":"Epigenetic Targeting of Granulin in Hepatoma Cells by Synthetic CRISPR dCas9 Epi\u2010Suppressors","volume":"11","author":"Wang H.","year":"2018","journal-title":"Molecular Therapy\u2014Nucleic Acids"},{"issue":"2","key":"e_1_2_18_81_1","first-page":"2441","article-title":"Dynamics of CRISPR\/Cas9\u2010Mediated Genomic Editing of the AXL Locus in Hepatocellular Carcinoma Cells","volume":"15","author":"Scharf I.","year":"2018","journal-title":"Oncology Letters"},{"issue":"2","key":"e_1_2_18_82_1","doi-asserted-by":"crossref","DOI":"10.1080\/22221751.2023.2276337","article-title":"CRISPR\/Cas13a\u2010Assisted Accurate and Portable Hepatitis D Virus RNA Detection","volume":"12","author":"Tian Y.","year":"2023","journal-title":"Emerging Microbes & Infections"},{"key":"e_1_2_18_83_1","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.omtm.2020.11.014","article-title":"CRISPR\u2010Cas9 Gene Editing of Hepatitis B Virus in Chronically Infected Humanized Mice","volume":"20","author":"Stone D.","year":"2021","journal-title":"Molecular Therapy\u2014Methods & Clinical Development"},{"issue":"1","key":"e_1_2_18_84_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.omtn.2023.102112","article-title":"Cytosine Base Editing Inhibits Hepatitis B Virus Replication and Reduces HBsAg Expression In\u00a0Vitro and In\u00a0Vivo","volume":"35","author":"Smekalova E. 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M.","year":"2015","journal-title":"Virology"},{"issue":"3","key":"e_1_2_18_88_1","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1006\/mthe.2001.0276","article-title":"Transduction of Liver Cells by Lentiviral Vectors: Analysis in Living Animals by Fluorescence Imaging","volume":"3","author":"Pfeifer A.","year":"2001","journal-title":"Molecular Therapy"},{"issue":"1","key":"e_1_2_18_89_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1089\/hgtb.2011.010","article-title":"Priming of Hepatocytes Enhances In\u00a0Vivo Liver Transduction With Lentiviral Vectors in Adult Mice","volume":"23","author":"Pichard V.","year":"2012","journal-title":"Human Gene Therapy Methods"},{"issue":"5","key":"e_1_2_18_90_1","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1161\/CIRCRESAHA.115.304351","article-title":"Permanent Alteration of PCSK9 With In\u00a0Vivo CRISPR\u2010Cas9 Genome Editing","volume":"115","author":"Ding Q.","year":"2014","journal-title":"Circulation Research"},{"issue":"10","key":"e_1_2_18_91_1","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1038\/nmeth.3993","article-title":"A Multifunctional AAV\u2010CRISPR\u2010Cas9 and Its Host Response","volume":"13","author":"Chew W. 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J.","year":"2015","journal-title":"Nano Letters"},{"issue":"2","key":"e_1_2_18_95_1","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/nbt.1733","article-title":"Expression of Therapeutic Proteins After Delivery of Chemically Modified mRNA in Mice","volume":"29","author":"Kormann M. S.","year":"2011","journal-title":"Nature Biotechnology"},{"issue":"3","key":"e_1_2_18_96_1","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1021\/acs.bioconjchem.6b00090","article-title":"Effects of Chemically Modified Messenger RNA on Protein Expression","volume":"27","author":"Li B.","year":"2016","journal-title":"Bioconjugate Chemistry"},{"issue":"3","key":"e_1_2_18_97_1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s00262-016-1800-2","article-title":"TCR Gene\u2010Modified T Cells Can Efficiently Treat Established Hepatitis C\u2010Associated Hepatocellular Carcinoma Tumors","volume":"65","author":"Spear T. T.","year":"2016","journal-title":"Cancer Immunology, Immunotherapy"},{"issue":"3","key":"e_1_2_18_98_1","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/nbt.3469","article-title":"A Dual AAV System Enables the Cas9\u2010Mediated Correction of a Metabolic Liver Disease in Newborn Mice","volume":"34","author":"Yang Y.","year":"2016","journal-title":"Nature Biotechnology"},{"issue":"4","key":"e_1_2_18_99_1","doi-asserted-by":"crossref","first-page":"2577","DOI":"10.1093\/nar\/gkt1074","article-title":"Phylogeny of Cas9 Determines Functional Exchangeability of Dual\u2010RNA and Cas9 Among Orthologous Type II CRISPR\u2010Cas Systems","volume":"42","author":"Fonfara I.","year":"2014","journal-title":"Nucleic Acids Research"},{"issue":"7546","key":"e_1_2_18_100_1","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/nature14299","article-title":"In Vivo Genome Editing Using \n                     Staphylococcus aureus\n                   Cas9","volume":"520","author":"Ran F. A.","year":"2015","journal-title":"Nature"},{"issue":"3","key":"e_1_2_18_101_1","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1016\/j.cell.2015.09.038","article-title":"Cpf1 Is a Single RNA\u2010Guided Endonuclease of a Class 2 CRISPR\u2010Cas System","volume":"163","author":"Zetsche B.","year":"2015","journal-title":"Cell"},{"issue":"5","key":"e_1_2_18_102_1","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.cell.2014.02.001","article-title":"Crystal Structure of Cas9 in Complex With Guide RNA and Target DNA","volume":"156","author":"Nishimasu H.","year":"2014","journal-title":"Cell"},{"issue":"3","key":"e_1_2_18_103_1","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.ijcard.2004.09.003","article-title":"One Year Transgene Expression With Adeno\u2010Associated Virus Cardiac Gene Transfer","volume":"100","author":"Woo Y. J.","year":"2005","journal-title":"International Journal of Cardiology"},{"issue":"9","key":"e_1_2_18_104_1","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1038\/mt.2016.172","article-title":"A Self\u2010Restricted CRISPR System to Reduce Off\u2010Target Effects","volume":"24","author":"Chen Y.","year":"2016","journal-title":"Molecular Therapy"},{"issue":"7488","key":"e_1_2_18_105_1","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1038\/nature12875","article-title":"Selection and Evaluation of Clinically Relevant AAV Variants in a Xenograft Liver Model","volume":"506","author":"Lisowski L.","year":"2014","journal-title":"Nature"},{"issue":"6","key":"e_1_2_18_106_1","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/j.celrep.2015.07.019","article-title":"In Silico Reconstruction of the Viral Evolutionary Lineage Yields a Potent Gene Therapy Vector","volume":"12","author":"Zinn E.","year":"2015","journal-title":"Cell Reports"},{"key":"e_1_2_18_107_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12896-015-0230-0","article-title":"Single Point Mutation in Adeno\u2010Associated Viral Vectors \u2010DJ Capsid Leads to Improvement for Gene Delivery In\u00a0Vivo","volume":"16","author":"Mao Y.","year":"2016","journal-title":"BMC Biotechnology"},{"issue":"5","key":"e_1_2_18_108_1","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1089\/hum.2010.243","article-title":"A Simple Method to Increase the Transduction Efficiency of Single\u2010Stranded Adeno\u2010Associated Virus Vectors In\u00a0Vitro and In\u00a0Vivo","volume":"22","author":"Ma W.","year":"2011","journal-title":"Human Gene Therapy"},{"issue":"8","key":"e_1_2_18_109_1","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 X.","year":"2015","journal-title":"Journal of General Virology"},{"issue":"11","key":"e_1_2_18_110_1","doi-asserted-by":"crossref","first-page":"2868","DOI":"10.1073\/pnas.1520244113","article-title":"Efficient Delivery of Genome\u2010Editing Proteins Using Bioreducible Lipid Nanoparticles","volume":"113","author":"Wang M.","year":"2016","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"e_1_2_18_111_1","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.virusres.2017.06.010","article-title":"The Potential and Challenges of CRISPR\u2010Cas in Eradication of Hepatitis B Virus Covalently Closed Circular DNA","volume":"244","author":"Yang H. C.","year":"2018","journal-title":"Virus Research"},{"issue":"5","key":"e_1_2_18_112_1","doi-asserted-by":"crossref","DOI":"10.1002\/iid3.866","article-title":"CRISPR\/Cas9 for Hepatitis B Virus Infection Treatment","volume":"11","author":"Cai B.","year":"2023","journal-title":"Immunity, Inflammation and Disease"},{"issue":"11","key":"e_1_2_18_113_1","doi-asserted-by":"crossref","first-page":"26077","DOI":"10.3390\/ijms161125950","article-title":"Application of CRISPR\/Cas9 Technology to HBV","volume":"16","author":"Lin G.","year":"2015","journal-title":"International Journal of Molecular Sciences"},{"issue":"1","key":"e_1_2_18_114_1","doi-asserted-by":"crossref","DOI":"10.3390\/v14010004","article-title":"Recent Progress and Future Prospective in HBV Cure by CRISPR\/Cas","volume":"14","author":"Yang Y. 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