ArticleMolecular therapy. Nucleic acids2022
Self-assembling short immunostimulatory duplex RNAs with broad-spectrum antiviral activity.
Article in Molecular therapy. Nucleic acids, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- Respiratory Organ-on-a-Chip for Disease Modeling: From Architecture to Functional Integration.Advanced healthcare materials · 2026Review
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- Proteolysis-targeting influenza vaccine strains induce broad-spectrum immunity and in vivo protection.Nature microbiology · 2025Article
- Therapeutic efficacy of a novel self-assembled immunostimulatory siRNA combining apoptosis promotion with RIG-I activation in gliomas.Journal of translational medicine · 2024Article
- Report of the Assay Guidance Workshop on 3-Dimensional Tissue Models for Antiviral Drug Development.The Journal of infectious diseases · 2023Article
- Organ-on-a-chip meets artificial intelligence in drug evaluation.Theranostics · 2023Review
- Review
- dsRNA as broad-spectrum antiviral therapeutics.Molecular therapy. Nucleic acids · 2022Article
- What Can an Organ-on-a-Chip Teach Us About Human Lung Pathophysiology?Physiology (Bethesda, Md.) · 2022Review
- Human organs-on-chips for disease modelling, drug development and personalized medicine.Nature reviews. Genetics · 2022Review
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22 authors at 5 institutions in 1 country.
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Abstract
The current coronavirus disease 2019 (COVID-19) pandemic highlights the need for broad-spectrum antiviral therapeutics. Here we describe a new class of self-assembling immunostimulatory short duplex RNAs that potently induce production of type I and type III interferon (IFN-I and IFN-III). These RNAs require a minimum of 20 base pairs, lack any sequence or structural characteristics of known immunostimulatory RNAs, and instead require a unique sequence motif (sense strand, 5'-C; antisense strand, 3'-GGG) that mediates end-to-end dimer self-assembly. The presence of terminal hydroxyl or monophosphate groups, blunt or overhanging ends, or terminal RNA or DNA bases did not affect their ability to induce IFN. Unlike previously described immunostimulatory small interfering RNAs (siRNAs), their activity is independent of Toll-like receptor (TLR) 7/8, but requires the RIG-I/IRF3 pathway that induces a more restricted antiviral response with a lower proinflammatory signature compared with immunostimulant poly(I:C). Immune stimulation mediated by these duplex RNAs results in broad-spectrum inhibition of infections by many respiratory viruses with pandemic potential, including severe acute respiratory syndrome coronavirus (SARS-CoV)-2, SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), human coronavirus (HCoV)-NL63, and influenza A virus in cell lines, human lung chips that mimic organ-level lung pathophysiology, and a mouse SARS-CoV-2 infection model. These short double-stranded RNAs (dsRNAs) can be manufactured easily, and thus potentially could be harnessed to produce broad-spectrum antiviral therapeutics.
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Registered trials
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