Evidence map›Paper›PMID 36945774›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023

Pseudoknot-targeting Cas13b combats SARS-CoV-2 infection by suppressing viral replication.

Daseuli Yu, Hee-Jeong Han, Jeonghye Yu, Jihye Kim, Gun-Hee Lee, Ju-Hee Yang, Byeong-Min Song, Dongseob Tark, Byeong-Sun Choi, Sang-Min Kang and 1 more

Abstract read
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

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  13. Small Molecules Targeting Viral RNA.International journal of molecular sciences · 2023
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Daseuli YuLife Science Research Institute, Korea Advanced Institute of Science and Technology, Daejeon, Republic of Korea.
Hee-Jeong HanLaboratory for Infectious Disease Prevention, Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Republic of Korea.
Jeonghye YuDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
Jihye KimDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea.
Gun-Hee LeeLaboratory for Infectious Disease Prevention, Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Republic of Korea.
Ju-Hee YangLaboratory for Infectious Disease Prevention, Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Republic of Korea.
Byeong-Min SongLaboratory for Infectious Disease Prevention, Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Republic of Korea.
Dongseob TarkLaboratory for Infectious Disease Prevention, Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Republic of Korea.
Byeong-Sun ChoiHonam Regional Center for Disease Control and Prevention, RCDC, Korea Disease Control and Prevention Agency, Gwangju 61947, Republic of Korea.
Sang-Min KangLaboratory for Infectious Disease Prevention, Korea Zoonosis Research Institute, Jeonbuk National University, Iksan 54531, Republic of Korea. Electronic address: sangminkang@jbnu.ac.kr.
Won Do HeoDepartment of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea; KAIST Institute for the BioCentury, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea. Electronic address: wondo@kaist.ac.kr.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

CRISPR-Cas13-mediated viral genome targeting is a novel strategy for defending against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants. Here, we generated mRNA-encoded Cas13b targeting the open reading frame 1b (ORF1b) region to effectively degrade the RNA-dependent RNA polymerase gene. Of the 12 designed CRISPR RNAs (crRNAs), those targeting the pseudoknot site upstream of ORF1b were found to be the most effective in suppressing SARS-CoV-2 propagation. Pseudoknot-targeting Cas13b reduced expression of the spike protein and attenuated viral replication by 99%. It also inhibited the replication of multiple SARS-CoV-2 variants, exhibiting broad potency. We validated the therapeutic efficacy of this system in SARS-CoV-2-infected hACE2 transgenic mice, demonstrating that crRNA treatment significantly reduced viral titers. Our findings suggest that the pseudoknot region is a strategic site for targeted genomic degradation of SARS-CoV-2. Hence, pseudoknot-targeting Cas13b could be a breakthrough therapy for overcoming infections by SARS-CoV-2 or other RNA viruses.

Indexed as

COVID-19AnimalsMiceRNA, ViralSARS-CoV-2Virus ReplicationRNA, Viralanti-SARS-CoV-2 drugmRNA-encoded CRISPR-Cas13 systempseudoknot regionviral frameshifting site

Identifiers

PMID36945774
PMCPMC10028249

What OpenQuestion holds

Textmetadata
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Registered trials

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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.