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Self-assembling short immunostimulatory duplex RNAs with broad spectrum antiviral activity
Longlong Si1, Haiqing Bai1, Crystal Yuri Oh1
1Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Biorxiv : the Preprint Server for Biology
|November 30, 2021
Summary
New short duplex RNAs trigger potent interferon production for broad-spectrum antiviral defense. These self-assembling RNAs offer a promising, low-cost therapeutic strategy against respiratory viruses like SARS-CoV-2.
Area of Science:
- Immunology
- Virology
- RNA Therapeutics
Background:
- The COVID-19 pandemic underscores the urgent need for broad-spectrum antiviral treatments.
- Current therapeutics often lack efficacy against diverse respiratory viruses.
Approach:
- Developed novel self-assembling short duplex RNAs (dsRNAs) that induce type I and III interferon (IFN-I/III) production.
- Identified a unique conserved sequence motif (5'-C/3'-GGG) essential for RNA self-assembly via Hoogsteen G-G base-pairing.
- Demonstrated IFN induction independent of TLR7/8, relying on the RIG-I/IRF3 pathway.
Key Points:
- These dsRNAs activate a restricted antiviral response with lower inflammation compared to poly(I:C).
- Effective against a wide range of respiratory viruses including SARS-CoV-2, MERS-CoV, influenza A, and HCoV-NL63.
- Activity is robust, unaffected by variations in terminal groups, end structure, or base composition.
Conclusions:
- Self-assembling dsRNAs represent a new class of potent immunostimulatory agents.
- This approach offers a potential low-cost, easily manufactured therapeutic strategy for diverse viral infections.
- The RIG-I/IRF3-mediated response provides broad-spectrum antiviral protection with reduced proinflammatory effects.
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