ArticlemBio2022
CRISPR-Cas9 Targeting of Hepatitis B Virus Covalently Closed Circular DNA Generates Transcriptionally Active Episomal Variants.
Article in mBio, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
34 citing papers in PubMed, 41 citations in OpenAlex.
- Development of an investigational epigenetic silencer therapy to transcriptionally inactivate viral DNA in chronic hepatitis B.Nature biomedical engineering · 2026Article
- AAV-mediated delivery of CRISPR/Cas9 targeting conserved overlapping ORFs efficiently suppresses HBV replication in hepatocyte models.Biotechnology reports (Amsterdam, Netherlands) · 2026Article
- Review
- Chromatin Accessibility-Guided Targeting Identifies Structurally Constrained Regions in HBV cccDNA and Suppresses Viral Replication.International journal of molecular sciences · 2026Article
- [Clinical significance and occurrence mechanism of hepatitis B virus DNA integration].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Multiplex gene editing suppresses random integration of hepatitis B virus DNA in chronically infected liver.Molecular therapy. Nucleic acids · 2026Article
- DNA and RNA editing for the therapy of human diseases: current status, challenges, and future prospects.Molecular biomedicine · 2026Review
- Insight into the Biology of Hepatitis B Virus and Recent Therapeutic Approaches.Current microbiology · 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
- Anticodon Engineered Transfer RNA (tRNAAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Highly stable Cas9 promotes HBV genome destruction by antagonizing HSC70-mediated degradation.Emerging microbes & infections · 2025Article
- Genomic medicine in hepatology: mechanisms and liver treatment strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- Drug development for chronic hepatitis B functional cure: Recent progress.World journal of hepatology · 2025Review
- The role of pioneering transcription factors, chromatin accessibility and epigenetic reprogramming in oncogenic viruses.Frontiers in microbiology · 2025Review
- Tackling hepatitis B Virus with CRISPR/Cas9: advances, challenges, and delivery strategies.Virus genes · 2024Review
- Engineered extracellular vesicles for delivering functional Cas9/gRNA to eliminate hepatitis B virus cccDNA and integration.Emerging microbes & infections · 2024Article
- Applications of CRISPR/Cas as a Toolbox for Hepatitis B Virus Detection and Therapeutics.Viruses · 2024Review
- Review
- Cytosine base editing inhibits hepatitis B virus replication and reduces HBsAg expressionMolecular therapy. Nucleic acids · 2024Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Chronic hepatitis B virus (HBV) infection persists due to the lack of therapies that effectively target the HBV covalently closed circular DNA (cccDNA). We used HBV-specific guide RNAs (gRNAs) and CRISPR-Cas9 and determined the fate of cccDNA after gene editing. We set up a ribonucleoprotein (RNP) delivery system in HBV-infected HepG2-NTCP cells. HBV parameters after Cas9 editing were analyzed. Southern blot (SB) analysis and DNA/RNA sequencing (DNA/RNA-seq) were performed to determine the consequences of cccDNA editing and transcriptional activity of mutated cccDNA. Treatment of infected cells with HBV-specific gRNAs showed that CRISPR-Cas9 can efficiently affect HBV replication. The appearance of episomal HBV DNA variants after dual gRNA treatment was observed by PCR, SB analysis, and DNA/RNA-seq. These transcriptionally active variants are the products of simultaneous Cas9-induced double-strand breaks in two target sites, followed by repair and religation of both short and long fragments. Following suppression of HBV DNA replicative intermediates by nucleoside analogs, mutations and formation of smaller transcriptionally active HBV variants were still observed, suggesting that established cccDNA is accessible to CRISPR-Cas9 editing. Targeting HBV DNA with CRISPR-Cas9 leads to cleavage followed by appearance of episomal HBV DNA variants. Effects induced by Cas9 were sustainable after RNP degradation/loss of detection, suggesting permanent changes in the HBV genome instead of transient effects due to transcriptional interference.
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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.