ArticleJournal of virology2004
Alternative approaches for efficient inhibition of hepatitis C virus RNA replication by small interfering RNAs.
Article in Journal of virology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed.
- Therapeutic Approaches of Viral Gene Silencing by Small Interfering RNA: Strategies to Prevent the Emergence of Antiviral Resistant Escape Mutants.Pharmaceuticals (Basel, Switzerland) · 2025Review
- A novel concept of human antiviral protection: It's all about RNA (Review).Biomedical reports · 2022Review
- An RNA Interference/Adeno-Associated Virus Vector-Based Combinatorial Gene Therapy Approach Against Hepatitis E Virus.Hepatology communications · 2022Article
- shRNA transgenic swine display resistance to infection with the foot-and-mouth disease virus.Scientific reports · 2021Article
- Consensus small interfering RNA targeted to stem-loops II and III of IRES structure of 5' UTR effectively inhibits virus replication and translation of HCV sub-genotype 4a isolates from Saudi Arabia.Saudi journal of biological sciences · 2021Article
- Small Interfering RNAs Are Highly Effective Inhibitors of Crimean-Congo Hemorrhagic Fever Virus Replication In Vitro.Molecules (Basel, Switzerland) · 2020Article
- TALEN/CRISPR-mediated engineering of a promoterless anti-viral RNAi hairpin into an endogenous miRNA locus.Nucleic acids research · 2017Article
- In Silico Design and Experimental Validation of siRNAs Targeting Conserved Regions of Multiple Hepatitis C Virus Genotypes.PloS one · 2016Article
- Alleviation of off-target effects from vector-encoded shRNAs via codelivered RNA decoys.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Review
- Inhibition of hepatitis C virus in chimeric mice by short synthetic hairpin RNAs: sequence analysis of surviving virus shows added selective pressure of combination therapy.Journal of virology · 2014Article
- RNAi-based inhibition of porcine reproductive and respiratory syndrome virus replication in transgenic pigs.Journal of biotechnology · 2014Article
- Formulated minimal-length synthetic small hairpin RNAs are potent inhibitors of hepatitis C virus in mice with humanized livers.Gastroenterology · 2014Article
- Inhibition of avian leukosis virus subgroup J replication by miRNA targeted against env.Virus genes · 2013Article
- Improving the effectiveness of artificial microRNA (amiR)-mediated resistance against Turnip mosaic virus by combining two amiRs or by targeting highly conserved viral genomic regions.Journal of virology · 2013Article
- Sigma-1 receptor regulates early steps of viral RNA replication at the onset of hepatitis C virus infection.Journal of virology · 2013Article
- Inhibition of HCV 5'-NTR and core expression by a small hairpin RNA delivered by a histone gene carrier, HPhA.International journal of medical sciences · 2013Article
- Ultradeep sequencing analysis of population dynamics of virus escape mutants in RNAi-mediated resistant plants.Molecular biology and evolution · 2012Article
- RNA interference with special reference to combating viruses of crustacea.Indian journal of virology : an official organ of Indian Virological Society · 2012Article
- All for one, one for all: new combinatorial RNAi therapies combat hepatitis C virus evolution.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
6 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Persistent infection with hepatitis C virus (HCV) is a leading cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. It has recently been shown that HCV RNA replication is susceptible to small interfering RNAs (siRNAs), but the antiviral activity of siRNAs depends very much on their complementarity to the target sequence. Thus, the high degree of sequence diversity between different HCV genotypes and the rapid evolution of new quasispecies is a major problem in the development of siRNA-based gene therapies. For this study, we developed two alternative strategies to overcome these obstacles. In one approach, we used endoribonuclease-prepared siRNAs (esiRNAs) to simultaneously target multiple sites of the viral genome. We show that esiRNAs directed against various regions of the HCV coding sequence as well as the 5' nontranslated region (5' NTR) efficiently block the replication of subgenomic and genomic HCV replicons. In an alternative approach, we generated pseudotyped retroviruses encoding short hairpin RNAs (shRNAs). A total of 12 shRNAs, most of them targeting highly conserved sequence motifs within the 5' NTR or the early core coding region, were analyzed for their antiviral activities. After the transduction of Huh-7 cells containing a subgenomic HCV replicon, we found that all shRNAs targeting sequences in domain IV or nearby coding sequences blocked viral replication. In contrast, only one of seven shRNAs targeting sequences in domain II or III had a similar degree of antiviral activity, indicating that large sections of the NTRs are resistant to RNA interference. Moreover, we show that naive Huh-7 cells that stably expressed certain 5' NTR-specific shRNAs were largely resistant to a challenge with HCV replicons. These results demonstrate that the retroviral transduction of HCV-specific shRNAs provides a new possibility for antiviral intervention.
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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.