ArticleProceedings of the National Academy of Sciences of the United States of America2012
Tiling genomes of pathogenic viruses identifies potent antiviral shRNAs and reveals a role for secondary structure in shRNA efficacy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Therapeutic Approaches of Viral Gene Silencing by Small Interfering RNA: Strategies to Prevent the Emergence of Antiviral Resistant Escape Mutants.Pharmaceuticals (Basel, Switzerland) · 2025Review
- From a genome-wide screen of RNAi molecules against SARS-CoV-2 to a validated broad-spectrum and potent prophylaxis.Communications biology · 2023Article
- Genome wide screen of RNAi molecules against SARS-CoV-2 creates a broadly potent prophylaxis.bioRxiv : the preprint server for biology · 2022Article
- Alternative polyadenylation confers Pten mRNAs stability and resistance to microRNAs.Nucleic acids research · 2018Article
- The sequence features that define efficient and specific hAGO2-dependent miRNA silencing guides.Nucleic acids research · 2018Article
- Argonaute proteins regulate HIV-1 multiply spliced RNA and viral production in a Dicer independent manner.Nucleic acids research · 2017Article
- Article
- Next-generation libraries for robust RNA interference-based genome-wide screens.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Multiplexing seven miRNA-Based shRNAs to suppress HIV replication.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Pseudo-Seq: Genome-Wide Detection of Pseudouridine Modifications in RNA.Methods in enzymology · 2015Article
- Inducible and reversible lentiviral and Recombination Mediated Cassette Exchange (RMCE) systems for controlling gene expression.PloS one · 2015Article
- HIV-1 RNAs are Not Part of the Argonaute 2 Associated RNA Interference Pathway in Macrophages.PloS one · 2015Article
- Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells.Nature · 2014Article
- In silico single strand melting curve: a new approach to identify nucleic acid polymorphisms in Totiviridae.BMC bioinformatics · 2014Article
- Replication of many human viruses is refractory to inhibition by endogenous cellular microRNAs.Journal of virology · 2014Article
- Genome-wide probing of RNA structure reveals active unfolding of mRNA structures in vivo.Nature · 2014Article
- Stable RNA interference rules for silencing.Nature cell biology · 2014Review
- Organic small hairpin RNAs (OshR): a do-it-yourself platform for transgene-based gene silencing.Methods (San Diego, Calif.) · 2013Article
- Inhibition of Dengue virus 2 replication by artificial micrornas targeting the conserved regions.Nucleic acid therapeutics · 2013Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
shRNAs can trigger effective silencing of gene expression in mammalian cells, thereby providing powerful tools for genetic studies, as well as potential therapeutic strategies. Specific shRNAs can interfere with the replication of pathogenic viruses and are currently being tested as antiviral therapies in clinical trials. However, this effort is hindered by our inability to systematically and accurately identify potent shRNAs for viral genomes. Here we apply a recently developed highly parallel sensor assay to identify potent shRNAs for HIV, hepatitis C virus (HCV), and influenza. We observe known and previously unknown sequence features that dictate shRNAs efficiency. Validation using HIV and HCV cell culture models demonstrates very high potency of the top-scoring shRNAs. Comparing our data with the secondary structure of HIV shows that shRNA efficacy is strongly affected by the secondary structure at the target RNA site. Artificially introducing secondary structure to the target site markedly reduces shRNA silencing. In addition, we observe that HCV has distinct sequence features that bias HCV-targeting shRNAs toward lower efficacy. Our results facilitate further development of shRNA based antiviral therapies and improve our understanding and ability to predict efficient shRNAs.
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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.