Evidence map›Paper›PMID 40829585›Full record

ArticleCell2025

Conversion of IscB and Cas9 into RNA-guided RNA editors.

Chengtao Xu, Xiaolin Niu, Haifeng Sun, Hao Yan, Weixin Tang, Ailong Ke

Abstract read
In one paragraph

Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Structural visualization of the molecular evolution of CRISPR-Cas9.Nature structural & molecular biology · 2026
    Article
  11. Directed evolution of an mResearch square · 2025
    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

6 authors.

Chengtao XuDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06512, USA.
Xiaolin NiuDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06512, USA.
Haifeng SunDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06512, USA.
Hao YanDepartment of Chemistry, The University of Chicago, Chicago, IL 60637, USA; Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
Weixin TangDepartment of Chemistry, The University of Chicago, Chicago, IL 60637, USA; Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA.
Ailong KeDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06512, USA. Electronic address: ailong.ke@yale.edu.

Funding

Mechanistic Investigation of RNA-Mediated Gene Regulation and ImmunityR35GM118174 · NIGMS · YALE UNIVERSITY · PI AILONG KE · 2016 to 2026
$7.9M
NIGMS NIH HHS R35 GM118174
6 · The paper itself

Abstract

RNA-guided RNA editing represents an attractive alternative to DNA editing. However, the prevailing tool, CRISPR-Cas13, has collateral RNA cleavage activity that causes undesirable cytotoxicity in human cells. Here, we report an ultracompact RNA-editing platform engineered from IscB, which has comparable or higher activity than Cas13 but without cytotoxicity concerns. We show that IscB, the evolutionary ancestor of Cas9, has an intrinsic affinity for complementary single-stranded (ss)DNA and RNA. This activity becomes dominant when its double-stranded DNA binding activity is switched off through the deletion of its target-adjacent motif domain. The resulting R-IscB is comparable to or better than Cas13, can efficiently alter splicing outcomes in human cells, and can further mediate trans-splicing to correct any mutation at the mRNA level. R-IscB also drives efficient A-to-I editing on mRNA when fused to adenosine deaminase acting on RNA 2 (ADAR2) and mediates cleavage-based mRNA knockdown upon HNH engineering. Finally, we show that the same approach converts some Cas9s to RNA-targeting tools.

Indexed as

CRISPR-Associated Protein 9CRISPR-Cas SystemsRNA EditingRNA, Guide, CRISPR-Cas SystemsAdenosine DeaminaseDNA, Single-StrandedGene EditingHEK293 CellsHumansRNA-Binding ProteinsRNA, MessengerTrans-SplicingAdenosine DeaminaseCRISPR-Associated Protein 9DNA, Single-StrandedRNA-Binding ProteinsRNA, Guide, CRISPR-Cas SystemsRNA, MessengerA-to-ICas13Cas9CmrCRISPRCsmIscBRNasetrans-splicing

Identifiers

PMID40829585
PMCPMC12798835

What OpenQuestion holds

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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.