ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
Targeting the hepatitis B cccDNA with a sequence-specific ARCUS nuclease to eliminate hepatitis B virus in vivo.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 45 citations in OpenAlex.
- Advanced gene editing technologies for oncology mechanisms, applications, and clinical implementation.Cancer gene therapy · 2026Review
- Development of an investigational epigenetic silencer therapy to transcriptionally inactivate viral DNA in chronic hepatitis B.Nature biomedical engineering · 2026Article
- Hepatitis B Virus: Epidemiology, Prophylaxis, Therapy, Clinical Outcomes, and Novel Therapeutic Directions.Biomolecules · 2026Review
- Review
- Multiplex gene editing suppresses random integration of hepatitis B virus DNA in chronically infected liver.Molecular therapy. Nucleic acids · 2026Article
- Review
- A Fluorescence Imaging- and Deep Learning-Based Approach for Detecting Hepatitis B Virus Integration into Host Genomes.Journal of imaging informatics in medicine · 2026Article
- Current and Emerging Therapeutic Strategies for the Treatment of Duchenne Muscular Dystrophy.Genes · 2026Review
- Transient muscle expression of mitoARCUS in mice leads to sustained reductions in pathogenic mtDNA and reduces fatigability.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- mRNA vaccines for HBV: Mechanisms, preclinical advances, and therapeutic clinical progress.Molecular therapy. Nucleic acids · 2026Review
- Adenine Base Editing Potently Suppresses Hepatitis B Surface Antigen Expression and Inhibits Hepatitis D Virus Release.bioRxiv : the preprint server for biology · 2026Article
- Review
- Advances in gene therapy for mitochondrial genetic disorders: current status and clinical implementation challenges.Journal of translational medicine · 2025Review
- Genome-edited allogeneic CAR-T cells: the next generation of cancer immunotherapies.Journal of hematology & oncology · 2025Review
- Genomic medicine in hepatology: mechanisms and liver treatment strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- RHO1-2 meganuclease gene editing targets human P23H rhodopsin-induced retinitis pigmentosa to rejuvenate rods and maintain cones.bioRxiv : the preprint server for biology · 2025Article
- High-efficiency homology-directed insertion into the genome using the engineered homing endonuclease ARCUS.Nucleic acids research · 2025Article
- Potential Applications of RNase P Ribozyme Against Hepatitis B Virus.Molecules (Basel, Switzerland) · 2025Review
- Advancing gene editing therapeutics: Clinical trials and innovative delivery systems across diverse diseases.Molecular therapy. Nucleic acids · 2025Review
- Serum factors create species-specific barriers to hepatic gene transfer by lipid nanoparticles in liver-humanized mice.Molecular therapy. Methods & clinical development · 2025Article
Corrections and comments
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Authors and funding
27 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Persistence of chronic hepatitis B (CHB) is attributed to maintenance of the intrahepatic pool of the viral covalently closed circular DNA (cccDNA), which serves as the transcriptional template for all viral gene products required for replication. Current nucleos(t)ide therapies for CHB prevent virus production and spread but have no direct impact on cccDNA or expression of viral genes. We describe a potential curative approach using a highly specific engineered ARCUS nuclease (ARCUS-POL) targeting the hepatitis B virus (HBV) genome. Transient ARCUS-POL expression in HBV-infected primary human hepatocytes produced substantial reductions in both cccDNA and hepatitis B surface antigen (HBsAg). To evaluate ARCUS-POL in vivo, we developed episomal adeno-associated virus (AAV) mouse and non-human primate (NHP) models containing a portion of the HBV genome serving as a surrogate for cccDNA. Clinically relevant delivery was achieved through systemic administration of lipid nanoparticles containing ARCUS-POL mRNA. In both mouse and NHP, we observed a significant decrease in total AAV copy number and high on-target indel frequency. In the case of the mouse model, which supports HBsAg expression, circulating surface antigen was durably reduced by 96%. Together, these data support a gene-editing approach for elimination of cccDNA toward an HBV cure.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.