ArticleEMBO molecular medicine2016
Blocking sense-strand activity improves potency, safety and specificity of anti-hepatitis B virus short hairpin RNA.
Article in EMBO molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Comparative genomics identifies small interfering RNA with activity against all five human betacoronaviruses.Genome medicine · 2026Article
- Long-term inhibition of Hepatitis B virus gene expression by a primary microrna expressing ancestral adeno-associated viral vector.Virology journal · 2025Review
- Review
- RNA Interference Therapeutics for Chronic Hepatitis B: Progress, Challenges, and Future Prospects.Microorganisms · 2024Review
- Multiscale modeling of HBV infection integrating intra- and intercellular viral propagation to analyze extracellular viral markers.PLoS computational biology · 2024Article
- An RNA Interference/Adeno-Associated Virus Vector-Based Combinatorial Gene Therapy Approach Against Hepatitis E Virus.Hepatology communications · 2022Article
- Advances in designing Adeno-associated viral vectors for development of anti-HBV gene therapeutics.Virology journal · 2021Review
- Article
- The evolution and clinical impact of hepatitis B virus genome diversity.Nature reviews. Gastroenterology & hepatology · 2020Review
- Hypoxic gene expression in chronic hepatitis B virus infected patients is not observed in state-of-the-art in vitro and mouse infection models.Scientific reports · 2020Article
- Review
- Enhanced Tailored MicroRNA Sponge Activity of RNA Pol II-Transcribed TuD Hairpins Relative to Ectopically Expressed ciRS7-Derived circRNAs.Molecular therapy. Nucleic acids · 2018Article
- Review
- The state of gene therapy research in Africa, its significance and implications for the future.Gene therapy · 2017Review
- Improved microRNA suppression by WPRE-linked tough decoy microRNA sponges.RNA (New York, N.Y.) · 2017Article
- Enhanced antiviral and antifibrotic effects of short hairpin RNAs targeting HBV and TGF-β in HBV-persistent mice.Scientific reports · 2017Article
- Sustained Inhibition of HBV Replication In Vivo after Systemic Injection of AAVs Encoding Artificial Antiviral Primary MicroRNAs.Molecular therapy. Nucleic acids · 2017Article
- Review
- TALEN/CRISPR-mediated engineering of a promoterless anti-viral RNAi hairpin into an endogenous miRNA locus.Nucleic acids research · 2017Article
- Blocking sense-strand activity improves potency, safety and specificity of anti-hepatitis B virus short hairpin RNA.EMBO molecular medicine · 2016Article
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis B virus (HBV) is a promising target for therapies based on RNA interference (RNAi) since it replicates via RNA transcripts that are vulnerable to RNAi silencing. Clinical translation of RNAi technology, however, requires improvements in potency, specificity and safety. To this end, we systematically compared different strategies to express anti-HBV short hairpin RNA (shRNA) in a pre-clinical immunocompetent hepatitis B mouse model. Using recombinant Adeno-associated virus (AAV) 8 vectors for delivery, we either (i) embedded the shRNA in an artificial mi(cro)RNA under a liver-specific promoter; (ii) co-expressed Argonaute-2, a rate-limiting cellular factor whose saturation with excess RNAi triggers can be toxic; or (iii) co-delivered a decoy ("TuD") directed against the shRNA sense strand to curb off-target gene regulation. Remarkably, all three strategies minimised adverse side effects as compared to a conventional shRNA vector that caused weight loss, liver damage and dysregulation of > 100 hepatic genes. Importantly, the novel AAV8 vector co-expressing anti-HBV shRNA and TuD outperformed all other strategies regarding efficiency and persistence of HBV knock-down, thus showing substantial promise for clinical translation.
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