Evidence map›Paper›PMID 37872368›Full record

ArticleNature biomedical engineering2024

Intrinsic targeting of host RNA by Cas13 constrains its utility.

Zexu Li, Zihan Li, Xiaolong Cheng, Shengnan Wang, Xiaofeng Wang, Shixin Ma, Zhiyan Lu, Han Zhang, Wenchang Zhao, Zhisong Chen and 5 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature biomedical engineering, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

21 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Reprogramming mRNA localization by targeted RNA-protein interference.bioRxiv : the preprint server for biology · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Characterization of RNA editing and gene therapy with a compact CRISPR-Cas13 in the retina.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  17. Article
  18. Article
  19. Article
  20. 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

15 authors at 2 institutions in 2 countries.

Zexu Li *Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, China.ORCID http://orcid.org/0000-0002-4685-4656
Zihan Li *Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, China.ORCID http://orcid.org/0000-0001-5082-9560
Xiaolong Cheng *Center for Genetic Medicine Research, Children's National Hospital, Washington, DC, USA.
Shengnan WangKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, China.
Xiaofeng WangKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, China.
Shixin MaKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, China.
Zhiyan LuKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, China.
Han ZhangKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, China.
Wenchang ZhaoKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, China.
Zhisong ChenKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, China.
Yingjia YaoKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, China.
Cheng ZhangKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, China.
Lumen ChaoCenter for Genetic Medicine Research, Children's National Hospital, Washington, DC, USA.
Wei LiCenter for Genetic Medicine Research, Children's National Hospital, Washington, DC, USA. wli2@childrensnational.org.ORCID http://orcid.org/0000-0002-2163-7903
Teng FeiKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, China. feiteng@mail.neu.edu.cn.ORCID http://orcid.org/0000-0001-9620-0450
Northeastern University · CNChildren's National · US

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32071441
6 · The paper itself

Abstract

Cas13 can be used for the knockdown, editing, imaging or detection of RNA and for RNA-based gene therapy. Here by using RNA immunoprecipitation sequencing, transcriptome profiling, biochemical analysis, high-throughput screening and machine learning, we show that Cas13 can intrinsically target host RNA in mammalian cells through previously unappreciated mechanisms. Different from its known cis/trans RNA-cleavage activity, Cas13 can also cleave host RNA via mechanisms that are transcript-specific, independent of the sequence of CRISPR RNA and dynamically dependent on the conformational state of Cas13, as we show for several Cas13-family effectors encoded in one-vector and two-vector lentiviral systems. Moreover, host genes involved in viral processes and whose transcripts are intrinsically targeted by Cas13 contribute to constraining the lentiviral delivery and expression of Cas13. Our findings offer guidance for the appropriate use of lentiviral Cas13 systems and highlight the need for caution regarding intrinsic RNA targeting in Cas13-based applications.

Indexed as

CRISPR-Cas SystemsRNAAnimalsGene Expression ProfilingGenetic TherapyLentivirusMammalsRNA

Identifiers

PMID37872368
OpenAlexW4387874003

What OpenQuestion holds

Textmetadata
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.