Evidence map›Paper›PMID 34845453›Full record

ArticlebioRxiv : the preprint server for biology2021

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

Longlong Si, Haiqing Bai, Crystal Yuri Oh, Tian Zhang, Fan Hong, Amanda Jiang, Yongxin Ye, Tristan X Jordan, James Logue, Marisa McGrath and 9 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

1 citing paper in PubMed, 6 citations in OpenAlex.

  1. The neural bases for timing of durations.Nature reviews. Neuroscience · 2022
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 4 institutions in 1 country.

Longlong SiWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Haiqing BaiWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Crystal Yuri OhWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Tian ZhangDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Fan HongWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Amanda JiangWyss Institute for Biologically Inspired Engineering, Harvard University, 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, 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, Boston, MA 02115, USA.
Atiq NuraniWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Wuji CaoWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Rachelle Prantil-BaunWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Steven P GygiDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Rani K PowersWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Matthew FriemanDepartment of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Benjamin R tenOeverDepartment of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Donald E IngberWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA.
Harvard University · USUniversity of Maryland, Baltimore · USBoston Children's Hospital · USIcahn School of Medicine at Mount Sinai · 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
NHLBI NIH HHS UH3 HL141797
6 · The paper itself

Abstract

The 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), in a wide range of human cell types. These RNAs require a minimum of 20 base pairs, lack any sequence or structural characteristics of known immunostimulatory RNAs, and instead require a unique conserved sequence motif (sense strand: 5'-C, antisense strand: 3'-GGG) that mediates end-to-end dimer self-assembly of these RNAs by Hoogsteen G-G base-pairing. 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 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, and influenza A, as well as the common cold virus HCoV-NL63 in both cell lines and human Lung Chips that mimic organ-level lung pathophysiology. These short dsRNAs can be manufactured easily, and thus potentially could be harnessed to produce broad-spectrum antiviral therapeutics at low cost.

Identifiers

PMID34845453
PMCPMC8629196
OpenAlexW3216840021

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.