ArticleHepatology communications2022
An RNA Interference/Adeno-Associated Virus Vector-Based Combinatorial Gene Therapy Approach Against Hepatitis E Virus.
Article in Hepatology communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Extra-Hepatic Manifestations of Hepatitis E Virus (HEV): A Narrative Review on Meningoencephalitis.Life (Basel, Switzerland) · 2026Review
- Hepatitis E virus replication is maintained in proliferative cells within the intestinal crypt.Science advances · 2026Article
- pH-responsive virus-drug conjugates for targeted PD-L1 silencing and enhanced cancer immunotherapy.Journal of nanobiotechnology · 2026Article
- Research Progress on Hepatitis E Virus Culture.Pathogens (Basel, Switzerland) · 2025Review
- An hepatitis B and D virus infection model using human pluripotent stem cell-derived hepatocytes.EMBO reports · 2024Article
- Combining RNA Interference and RIG-I Activation to Inhibit Hepatitis E Virus Replication.Viruses · 2024Article
- Viral hepatitis E: Clinical manifestations, treatment, and prevention.Liver research (Beijing, China) · 2024Review
- A genome-wide CRISPR/Cas9 screen identifies a role for Rab5A and early endosomes in hepatitis E virus replication.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The prevention strategies of swine viruses related to xenotransplantation.Virology journal · 2023Review
- Expanding the Hepatitis E Virus Toolbox: Selectable Replicons and Recombinant Reporter Genomes.Viruses · 2023Review
- Identification of Plant Peptides as Novel Inhibitors of Orthohepevirus A (HEV) Capsid Protein by Virtual Screening.Molecules (Basel, Switzerland) · 2023Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis E virus (HEV) is a major public health problem with limited therapeutic options. Here, we engineered adeno-associated viral vectors of serotype 6 (AAV6) to express short hairpin RNAs (shRNAs) against HEV transcripts with the prospect of down-regulating HEV replication in vivo. We designed 20 different shRNAs, targeting the genome of the HEV genotype 3 (GT3) Kernow-C1 p6 strain, for delivery upon AAV6 transduction. Using an original selectable HEV GT3 reporter replicon, we identified three shRNAs that efficiently down-regulated HEV replication. We further confirmed their inhibitory potency with full-length HEV infection. Seventy-two hours following transduction, HEV replication in both systems decreased by up to 95%. The three most potent inhibitory shRNAs identified were directed against the methyltransferase domain, the junction region between the open reading frames (ORFs), and the 3´ end of ORF2. Targeting all three regions by multiplexing the shRNAs further enhanced their inhibitory potency over a prolonged period of up to 21 days following transduction. Conclusion: Combining RNA interference and AAV vector-based gene therapy has great potential for suppressing HEV replication. Our strategy to target the viral RNA with multiplexed shRNAs should help to counteract viral escape through mutations. Considering the widely documented safety of AAV vector-based gene therapies, our approach is, in principle, amenable to clinical translation.
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Registered trials
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