ArticleCellular and molecular life sciences : CMLS2019
Orthologous CRISPR/Cas9 systems for specific and efficient degradation of covalently closed circular DNA of hepatitis B virus.
Article in Cellular and molecular life sciences : CMLS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 85 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
- Broad-acting antivirals: the pursuit of pan-viral therapeutics in the era of pandemics.Journal of virology · 2026Review
- 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
- Chronic Hepatitis B: Current Management and Future Directions.Diseases (Basel, Switzerland) · 2025Review
- Potential Applications of RNase P Ribozyme Against Hepatitis B Virus.Molecules (Basel, Switzerland) · 2025Review
- Biologics-based technologies for highly efficient and targeted RNA delivery.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Tackling hepatitis B Virus with CRISPR/Cas9: advances, challenges, and delivery strategies.Virus genes · 2024Review
- Review
- Extracellular Vesicles in Viral Liver Diseases.Viruses · 2024Review
- Applications of CRISPR/Cas as a Toolbox for Hepatitis B Virus Detection and Therapeutics.Viruses · 2024Review
- Basic Guide for Approaching Drug Delivery with Extracellular Vesicles.International journal of molecular sciences · 2024Review
- Perspective on Emerging Therapies to Achieve Functional Cure of Chronic Hepatitis B.Current hepatology reports · 2024Article
- The potential of HBV cure: an overview of CRISPR-mediated HBV gene disruption.Frontiers in genome editing · 2024Review
- Review
- The role of HBV cccDNA in occult hepatitis B virus infection.Molecular and cellular biochemistry · 2023Review
- Article
- Synthetic gRNA/Cas9 ribonucleoprotein targeting HBV DNA inhibits viral replication.Journal of medical virology · 2023Article
- Transient and tunable CRISPRa regulation of APOBEC/AID genes for targeting hepatitis B virus.Molecular therapy. Nucleic acids · 2023Article
- Depleting hepatitis B virus relaxed circular DNA is necessary for resolution of infection by CRISPR-Cas9.Molecular therapy. Nucleic acids · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is the major cause of viral persistence and chronic hepatitis B. CRISPR/Cas9 nucleases can specifically target HBV cccDNA for decay, but off-target effects of nucleases in the human genome limit their clinical utility. CRISPR/Cas9 systems from four different species were co-expressed in cell lines with guide RNAs targeting conserved regions of the HBV genome. CRISPR/Cas9 systems from Streptococcus pyogenes (Sp) and Streptococcus thermophilus (St) targeting conserved regions of the HBV genome blocked HBV replication and, most importantly, resulted in degradation of over 90% of HBV cccDNA by 6 days post-transfection. Degradation of HBV cccDNA was impaired by inhibition of non-homologous end-joining pathway and resulted in an erroneous repair of HBV cccDNA. HBV cccDNA methylation also affected antiviral activity of CRISPR/Cas9. Single-nucleotide HBV genetic variants did not impact anti-HBV activity of St CRISPR/Cas9, suggesting its utility in targeting many HBV variants. However, two or more mismatches impaired or blocked CRISPR/Cas9 activity, indicating that host DNA will not likely be targeted. Deep sequencing revealed that Sp CRISPR/Cas9 induced off-target mutagenesis, whereas St CRISPR/Cas9 had no effect on the host genome. St CRISPR/Cas9 system represents the safest system with high anti-HBV activity.
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What OpenQuestion holds
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.