ArticlePloS one2016
In Silico Design and Experimental Validation of siRNAs Targeting Conserved Regions of Multiple Hepatitis C Virus Genotypes.
Article in PloS one, 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, 64 citations in OpenAlex.
- RNAi-based therapeutics targeting the F gene in human metapneumovirus: An in-silico approach.Journal, genetic engineering & biotechnology · 2026Article
- An LNP antiviral siRNA drug cocktail delivered intranasally is effective against a range of respiratory viruses.Virology journal · 2026Article
- HMPV-TherResDB: Comprehensive human metapneumovirus (HMPV) database for sequence-structure annotations, vaccine resources, and therapeutics research.Virus research · 2026Article
- Genomic medicine in hepatology: mechanisms and liver treatment strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- Therapeutic Approaches of Viral Gene Silencing by Small Interfering RNA: Strategies to Prevent the Emergence of Antiviral Resistant Escape Mutants.Pharmaceuticals (Basel, Switzerland) · 2025Review
- In Silico and In Vitro development of novel small interfering RNAs (siRNAs) to inhibit SARS-CoV-2.Computational and structural biotechnology journal · 2025Article
- Development, Design, and Application of Efficient siRNAs Against Cotton Leaf Curl Virus-Betasatellite Complex to Mediate Resistance Against Cotton Leaf Curl Disease.Indian journal of microbiology · 2024Article
- An ncRNA transcriptomics-based approach to design siRNA molecules against SARS-CoV-2 double membrane vesicle formation and accessory genes.BMC infectious diseases · 2023Article
- Small interfering RNA (siRNA)-based therapeutic applications against viruses: principles, potential, and challenges.Journal of biomedical science · 2023Review
- Delivery of siRNAs against MERS-CoV in Vero and HEK-293 cells: A comparative evaluation of transfection reagents.Journal of King Saud University. Science · 2023Article
- Computational Design and Experimental Evaluation of MERS-CoV siRNAs in Selected Cell Lines.Diagnostics (Basel, Switzerland) · 2023Article
- Computational study and design of effective siRNAs to silence structural proteins associated genes of Indian SARS-CoV-2 strains.Computational biology and chemistry · 2022Article
- A Comprehensive Computational Investigation into the Conserved Virulent Proteins ofMolecules (Basel, Switzerland) · 2022Article
- An in-silico approach to design potential siRNAs against the ORF57 of Kaposi's sarcoma-associated herpesvirus.Genomics & informatics · 2021Article
- Designing an effective therapeutic siRNA to silence RdRp gene of SARS-CoV-2.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2021Article
- In Vitro Inhibitory Analysis of Rationally Designed siRNAs against MERS-CoV Replication in Huh7 Cells.Molecules (Basel, Switzerland) · 2021Article
- Article
- Bioinformatics analysis reveals four major hexon variants of human adenovirus type-3 (HAdV-3) as the potential strains for development of vaccine and siRNA-based therapeutics against HAdV-3 respiratory infections.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2020Article
- Article
- Highly efficacious antiviral protection of plants by small interfering RNAs identified in vitro.Nucleic acids research · 2019Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNA interference (RNAi) is a post-transcriptional gene silencing mechanism that mediates the sequence-specific degradation of targeted RNA and thus provides a tremendous opportunity for development of oligonucleotide-based drugs. Here, we report on the design and validation of small interfering RNAs (siRNAs) targeting highly conserved regions of the hepatitis C virus (HCV) genome. To aim for therapeutic applications by optimizing the RNAi efficacy and reducing potential side effects, we considered different factors such as target RNA variations, thermodynamics and accessibility of the siRNA and target RNA, and off-target effects. This aim was achieved using an in silico design and selection protocol complemented by an automated MysiRNA-Designer pipeline. The protocol included the design and filtration of siRNAs targeting highly conserved and accessible regions within the HCV internal ribosome entry site, and adjacent core sequences of the viral genome with high-ranking efficacy scores. Off-target analysis excluded siRNAs with potential binding to human mRNAs. Under this strict selection process, two siRNAs (HCV353 and HCV258) were selected based on their predicted high specificity and potency. These siRNAs were tested for antiviral efficacy in HCV genotype 1 and 2 replicon cell lines. Both in silico-designed siRNAs efficiently inhibited HCV RNA replication, even at low concentrations and for short exposure times (24h); they also exceeded the antiviral potencies of reference siRNAs targeting HCV. Furthermore, HCV353 and HCV258 siRNAs also inhibited replication of patient-derived HCV genotype 4 isolates in infected Huh-7 cells. Prolonged treatment of HCV replicon cells with HCV353 did not result in the appearance of escape mutant viruses. Taken together, these results reveal the accuracy and strength of our integrated siRNA design and selection protocols. These protocols could be used to design highly potent and specific RNAi-based therapeutic oligonucleotide interventions.
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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.