ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Inactivation of hepatitis B virus replication in cultured cells and in vivo with engineered transcription activator-like effector nucleases.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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Who cites it
101 citing papers in PubMed.
- Pathogenesis, prevention, and therapeutic advances in hepatitis B, C, and D.Virology journal · 2025Review
- Article
- Current trends in gene therapy to treat inherited disorders of the brain.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Generating mRNA Encoding Anti-HBV Designer Epigenome Modifiers.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Prospects of viral vector-mediated delivery of sequences encoding anti-HBV designer endonucleases.Gene therapy · 2025Review
- The impact of integrated hepatitis B virus DNA on oncogenesis and antiviral therapy.Biomarker research · 2024Review
- The potential of HBV cure: an overview of CRISPR-mediated HBV gene disruption.Frontiers in genome editing · 2024Review
- Novel Approaches to Inhibition of HBsAg Expression from cccDNA and Chromosomal Integrants: A Review.Journal of clinical and translational hepatology · 2023Review
- HBV Vaccines: Advances and Development.Vaccines · 2023Review
- AAV Immunotoxicity: Implications in Anti-HBV Gene Therapy.Microorganisms · 2023Review
- Review
- Hepatitis B Virus Epsilon (ε) RNA Element: Dynamic Regulator of Viral Replication and Attractive Therapeutic Target.Viruses · 2023Review
- TRIM26 positively affects hepatitis B virus replication by inhibiting proteasome-dependent degradation of viral core protein.Scientific reports · 2023Article
- HBV Infection and Host Interactions: The Role in Viral Persistence and Oncogenesis.International journal of molecular sciences · 2023Review
- Early Subcellular Hepatocellular Alterations in Mice Post Hydrodynamic Transfection: An Explorative Study.Cancers · 2023Article
- The progress of molecules and strategies for the treatment of HBV infection.Frontiers in cellular and infection microbiology · 2023Review
- Gene Editing Technologies to Target HBV cccDNA.Viruses · 2022Review
- Review
- Review
- Hepatitis B Virus Research in South Africa.Viruses · 2022Review
41 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors.
Funding
Abstract
Chronic hepatitis B virus (HBV) infection remains an important global health problem. Stability of the episomal covalently closed circular HBV DNA (cccDNA) is largely responsible for the modest curative efficacy of available therapy. Since licensed anti-HBV drugs have a post-transcriptional mechanism of action, disabling cccDNA is potentially of therapeutic benefit. To develop this approach, we engineered mutagenic transcription activator-like effector nucleases (TALENs) that target four HBV-specific sites within the viral genome. TALENs with cognate sequences in the S or C open-reading frames (ORFs) efficiently disrupted sequences at the intended sites and suppressed markers of viral replication. Following triple transfection of cultured HepG2.2.15 cells under mildly hypothermic conditions, the S TALEN caused targeted mutation in ~35% of cccDNA molecules. Markers of viral replication were also inhibited in vivo in a murine hydrodynamic injection model of HBV replication. HBV target sites within S and C ORFs of the injected HBV DNA were mutated without evidence of toxicity. These findings are the first to demonstrate a targeted nuclease-mediated disruption of HBV cccDNA. Efficacy in vivo also indicates that these engineered nucleases have potential for use in treatment of chronic HBV infection.
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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 OpenQuestion graph.