ArticleMolecular therapy : the journal of the American Society of Gene Therapy2016
Complete Spectrum of CRISPR/Cas9-induced Mutations on HBV cccDNA.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
What it found
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Who cites it
79 citing papers in PubMed, 135 citations in OpenAlex.
- AAV-mediated delivery of CRISPR/Cas9 targeting conserved overlapping ORFs efficiently suppresses HBV replication in hepatocyte models.Biotechnology reports (Amsterdam, Netherlands) · 2026Article
- Review
- Disrupting Viral Persistence: CRISPR/Cas9-Based Strategies for Hepatitis B and C Treatment, and Challenges.Journal of cellular and molecular medicine · 2026Review
- Suppression of HBV replication and expression by CRISPR/Cas9 ribonucleoproteins.Antiviral research · 2026Article
- Innate immune recognition and evasion strategies of hepatitis B virus: from DNA to RNA and viral proteins.Frontiers in immunology · 2026Review
- Hepatitis B functional cure: Current and future perspective.World journal of hepatology · 2025Review
- Genomic medicine in hepatology: mechanisms and liver treatment strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- Applications of CRISPR/Cas as a Toolbox for Hepatitis B Virus Detection and Therapeutics.Viruses · 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
- Viral vectors and extracellular vesicles: innate delivery systems utilized in CRISPR/Cas-mediated cancer therapy.Cancer gene therapy · 2023Review
- Synthetic gRNA/Cas9 ribonucleoprotein targeting HBV DNA inhibits viral replication.Journal of medical virology · 2023Article
- Current and novel modalities for management of chronic hepatitis B infection.World journal of hepatology · 2023Review
- CRISPR/Cas9 for hepatitis B virus infection treatment.Immunity, inflammation and disease · 2023Review
- Review
- Depleting hepatitis B virus relaxed circular DNA is necessary for resolution of infection by CRISPR-Cas9.Molecular therapy. Nucleic acids · 2023Article
- Advances in CRISPR therapeutics.Nature reviews. Nephrology · 2023Review
- Novel therapeutic strategies for chronic hepatitis B.Virulence · 2022Review
- Gene Editing Technologies to Target HBV cccDNA.Viruses · 2022Review
- Review
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Hepatitis B virus (HBV) causes chronic infections that cannot yet be cured. The virus persists in infected hepatocytes, because covalently closed circular DNA (cccDNA), the template for the transcription of viral RNAs, is stable in nondividing cells. Antiviral therapies with nucleoside analogues inhibit HBV DNA synthesis in capsids in the cytoplasm of infected hepatocytes, but do not destroy nuclear cccDNA. Because over 200 million people are still infected, a cure for chronic hepatitis B (CHB) has become one of the major challenges in antiviral therapy. As a first step toward the development of curative therapies, we previously demonstrated that the CRISPR/Cas9 system can be used to functionally inactivate cccDNA derived from infectious HBV. Moreover, some evidence suggests that certain cytokines might induce an APOBEC-mediated cascade leading to the destruction of cccDNA. In this report we investigated whether a combination of the two mechanisms could act synergistically to inactivate cccDNA. Using next generation sequencing (NGS), we determined the complete spectrum of mutations in cccDNA following Cas9 cleavage and repair by nonhomologous end joining (NHEJ). We found that over 90% of HBV DNA was cleaved by Cas9. In addition our results showed that editing of HBV DNA after Cas9 cleavage is at least 15,000 times more efficient that APOBEC-mediated cytosine deamination following treatment of infected cells with interferon alpha (IFNα). We also found that a previously used method to detect cytosine deaminated DNA, termed 3D-PCR, overestimates the amount and frequency of edited HBV DNA. Taken together, our results demonstrated that the CRISPR/Cas9 system is so far the best method to functionally inactivate HBV cccDNA and provide a cure for CHB.
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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.