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dc.contributor.authorSi, Longlong
dc.contributor.authorBai, Haiqing
dc.contributor.authorOh, Crystal Yuri
dc.contributor.authorJiang, Amanda
dc.contributor.authorHong, Fan
dc.contributor.authorZhang, Tian
dc.contributor.authorYe, Yongxin
dc.contributor.authorJordan, Tristan X
dc.contributor.authorLogue, James
dc.contributor.authorMcGrath, Marisa
dc.contributor.authorBelgur, Chaitra
dc.contributor.authorCalderon, Karina
dc.contributor.authorNurani, Atiq
dc.contributor.authorCao, Wuji
dc.contributor.authorCarlson, Kenneth E
dc.contributor.authorPrantil-Baun, Rachelle
dc.contributor.authorGygi, Steven P
dc.contributor.authorYang, Dong
dc.contributor.authorJonsson, Colleen B
dc.contributor.authortenOever, Benjamin R
dc.contributor.authorFrieman, Matthew
dc.contributor.authorIngber, Donald E
dc.date.accessioned2022-08-31T17:36:10Z
dc.date.available2022-08-31T17:36:10Z
dc.date.issued2022-08-24
dc.identifier.urihttp://hdl.handle.net/10713/19648
dc.description.abstractThe current 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 siRNAs, their activity is independent of TLR7/8, 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 SARS-CoV-2, SARS-CoV, MERS-CoV, 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 dsRNAs can be manufactured easily, and thus potentially could be harnessed to produce broad-spectrum antiviral therapeutics.en_US
dc.description.urihttps://doi.org/10.1016/j.omtn.2022.08.031en_US
dc.language.isoenen_US
dc.publisherCell Pressen_US
dc.relation.ispartofMolecular Therapy Nucleic Acidsen_US
dc.rights© 2022 The Author(s).en_US
dc.titleSelf-assembling short immunostimulatory duplex RNAs with broad spectrum antiviral activity.en_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.omtn.2022.08.031
dc.identifier.pmid36032397
dc.source.journaltitleMolecular therapy. Nucleic acids
dc.source.countryUnited States


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