Evidence map›Paper›PMID 36726140›Full record

ArticleGenome biology2023

The collateral activity of RfxCas13d can induce lethality in a RfxCas13d knock-in mouse model.

Yunfei Li, Junjie Xu, Xuefei Guo, Zhiwei Li, Lili Cao, Shengde Liu, Ying Guo, Guodong Wang, Yujie Luo, Zeming Zhang and 14 more

Open access · goldAbstract read
In one paragraph

Article in Genome biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
11.2field-weighted citation impact, top 1% 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

47 citing papers in PubMed, 73 citations in OpenAlex.

  1. Article
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  3. Programmable RNA NAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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  5. Versatile CRISPR-Cas Tools for Gene Regulation in Zebrafish via an Enhanced Q Binary System.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  6. Article
  7. Article
  8. Precise RNA targeting with CRISPR-Cas13d.Nature biotechnology · 2026
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Precise progerin targeting using RfxCas13d: A therapeutic avenue for Hutchinson-Gilford progeria syndrome.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  16. Review
  17. CRISPR Technology and Its Emerging Applications.Genomics, proteomics & bioinformatics · 2025
    Review
  18. Article
  19. Article
  20. Article
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

24 authors at 6 institutions in 1 country.

Yunfei Li *Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, 100191, China. 1711110048@bjmu.edu.cn.ORCID 0000-0003-0595-2484
Junjie Xu *National Institute of Biological Sciences, Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, 102206, China.
Xuefei Guo *Department of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, 100191, China.
Zhiwei Li *School of Life Sciences, Institute of Life Sciences and Green Development, Hebei University, Baoding, 071002, Hebei, China.
Lili CaoBeijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, 100101, China.
Shengde LiuDepartment of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute, Beijing, 100142, China.
Ying GuoNational Institute of Biological Sciences, Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, 102206, China.
Guodong WangNational Institute of Biological Sciences, Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, 102206, China.
Yujie LuoDepartment of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, 100191, China.
Zeming ZhangDepartment of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, 100191, China.
Xuemei WeiDepartment of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, 100191, China.
Yingchi ZhaoDepartment of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, 100191, China.
Tongtong LiuDepartment of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, 100191, China.
Xiao WangDepartment of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, 100191, China.
Huawei XiaDepartment of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, 100191, China.
Ming KuangDepartment of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, 100191, China.
Qirui GuoDepartment of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, 100191, China.
Junhong LiDepartment of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, 100191, China.
Luoying ChenDepartment of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, 100191, China.
Yibing WangNational Institute of Biological Sciences, Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, 102206, China.
Qi LiNational Institute of Biological Sciences, Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, 102206, China.
Fengchao WangNational Institute of Biological Sciences, Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, 102206, China.
Qinghua LiuNational Institute of Biological Sciences, Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing, 102206, China. liuqinghua@nibs.ac.cn.
Fuping YouDepartment of Immunology, School of Basic Medical Sciences, Beijing Key Laboratory of Tumor Systems Biology, Institute of Systems Biomedicine, Peking University Health Science Center, Beijing, 100191, China. fupingyou@hsc.pku.edu.cn.
Peking University · CNTsinghua University · CNBeijing Normal University · CNChinese Academy of Sciences · CNHebei University · CNNational Institute of Biological Sciences, Beijing · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe CRISPR-Cas13 system is an RNA-guided RNA-targeting system and has been widely used in transcriptome engineering with potentially important clinical applications. However, it is still controversial whether Cas13 exhibits collateral activity in mammalian cells.

resultsHere, we find that knocking down gene expression using RfxCas13d in the adult brain neurons caused death of mice, which may result from the collateral activity of RfxCas13d rather than the loss of target gene function or off-target effects. Mechanistically, we show that RfxCas13d exhibits collateral activity in mammalian cells, which is positively correlated with the abundance of target RNA. The collateral activity of RfxCas13d could cleave 28s rRNA into two fragments, leading to translation attenuation and activation of the ZAKα-JNK/p38-immediate early gene pathway.

conclusionsThese findings provide new mechanistic insights into the collateral activity of RfxCas13d in mammalian cells and warn that the biosafety of the CRISPR-Cas13 system needs further evaluation before application to clinical treatments.

Indexed as

CRISPR-Cas SystemsRNAAnimalsMAP Kinase Signaling SystemMiceTranscriptomeRNA28s rRNA cleavageCollateral activityDeath of miceRfxCas13d

Identifiers

PMID36726140
PMCPMC9893547
OpenAlexW4318817249

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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.