Evidence map›Paper›PMID 36032397›Full record

ArticleMolecular therapy. Nucleic acids2022

Self-assembling short immunostimulatory duplex RNAs with broad-spectrum antiviral activity.

Longlong Si, Haiqing Bai, Crystal Yuri Oh, Amanda Jiang, Fan Hong, Tian Zhang, Yongxin Ye, Tristan X Jordan, James Logue, Marisa McGrath and 12 more

Open access · goldAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.4field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 18 citations in OpenAlex.

  1. Review
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  8. dsRNA as broad-spectrum antiviral therapeutics.Molecular therapy. Nucleic acids · 2022
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 5 institutions in 1 country.

Longlong SiWyss Institute for Biologically Inspired Engineering, Harvard University, CLSB5, 3 Blackfan Circle, Boston, MA 02115, USA.
Haiqing BaiWyss Institute for Biologically Inspired Engineering, Harvard University, CLSB5, 3 Blackfan Circle, Boston, MA 02115, USA.
Crystal Yuri OhWyss Institute for Biologically Inspired Engineering, Harvard University, CLSB5, 3 Blackfan Circle, Boston, MA 02115, USA.
Amanda JiangWyss Institute for Biologically Inspired Engineering, Harvard University, CLSB5, 3 Blackfan Circle, Boston, MA 02115, USA.
Fan HongWyss Institute for Biologically Inspired Engineering, Harvard University, CLSB5, 3 Blackfan Circle, Boston, MA 02115, USA.
Tian ZhangDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Yongxin YeDepartment of Genetics, Harvard Medical School, Boston, MA 02155, USA.
Tristan X JordanDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
James LogueDepartment of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Marisa McGrathDepartment of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Chaitra BelgurWyss Institute for Biologically Inspired Engineering, Harvard University, CLSB5, 3 Blackfan Circle, Boston, MA 02115, USA.
Karina CalderonWyss Institute for Biologically Inspired Engineering, Harvard University, CLSB5, 3 Blackfan Circle, Boston, MA 02115, USA.
Atiq NuraniWyss Institute for Biologically Inspired Engineering, Harvard University, CLSB5, 3 Blackfan Circle, Boston, MA 02115, USA.
Wuji CaoWyss Institute for Biologically Inspired Engineering, Harvard University, CLSB5, 3 Blackfan Circle, Boston, MA 02115, USA.
Kenneth E CarlsonWyss Institute for Biologically Inspired Engineering, Harvard University, CLSB5, 3 Blackfan Circle, Boston, MA 02115, USA.
Rachelle Prantil-BaunWyss Institute for Biologically Inspired Engineering, Harvard University, CLSB5, 3 Blackfan Circle, Boston, MA 02115, USA.
Steven P GygiDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Dong YangRegional Biocontainment Laboratory, The University of Tennessee Health Science Center, Memphis, TN 38105, USA.
Colleen B JonssonDepartment of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38105, USA.
Benjamin R tenOeverDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Matthew FriemanDepartment of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Donald E IngberWyss Institute for Biologically Inspired Engineering, Harvard University, CLSB5, 3 Blackfan Circle, Boston, MA 02115, USA.
Harvard University · USUniversity of Maryland, Baltimore · USBoston Children's Hospital · USIcahn School of Medicine at Mount Sinai · USUniversity of Tennessee Health Science Center · US

Funding

Lung-on-a-Chip Disease Models for Efficacy Testing (COVID-19 Competitive Revision)UH3HL141797 · NHLBI · HARVARD UNIVERSITY · PI INGBER, DONALD E · 2019 to 2021
$5.2M
A new multi-pathway kinase activity assay applied to compound library screening in cancer biologyK99CA273170 · NCI · HARVARD MEDICAL SCHOOL · PI ZHANG, TIAN · 2022 to 2022
$117k
NCI NIH HHS K99 CA273170NHLBI NIH HHS UH3 HL141797
6 · The paper itself

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.

Indexed as

antiviral therapeuticHoogsteen G-G base pairingimmunostimulatory RNAinfluenzainterferonMT: Oligonucleotidesorgan on a chipRIG-ISARS-CoV-2Therapies and Applications

Identifiers

PMID36032397
PMCPMC9398551
OpenAlexW4292849308

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.