Evidence map›Paper›PMID 38977787›Full record

ArticleNature chemical biology2024

Assessing and engineering the IscB-ωRNA system for programmed genome editing.

Hao Yan, Xiaoqing Tan, Siyuan Zou, Yihong Sun, Ailong Ke, Weixin Tang

Abstract read
In one paragraph

Article in Nature chemical biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing 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

30 citing papers in PubMed.

  1. Engineered Transformer Base Editor with Enhanced Editing Efficiency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  2. Review
  3. Article
  4. Compact 9dBEs Enable Efficient and Precise Genome Editing in Mammalian Cells and In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Structural visualization of the molecular evolution of CRISPR-Cas9.Nature structural & molecular biology · 2026
    Article
  14. Article
  15. Article
  16. Article
  17. Stepwise DNA unwinding gates TnpB genome-editing activity.bioRxiv : the preprint server for biology · 2026
    Article
  18. Article
  19. Review
  20. Highly efficient genome editing inSynthetic and systems biotechnology · 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.

Hao YanDepartment of Chemistry, The University of Chicago, Chicago, IL, USA.
Xiaoqing TanDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.ORCID http://orcid.org/0000-0002-1475-8125
Siyuan ZouDepartment of Chemistry, The University of Chicago, Chicago, IL, USA.ORCID http://orcid.org/0009-0005-7771-3644
Yihong SunDepartment of Chemistry, The University of Chicago, Chicago, IL, USA.ORCID http://orcid.org/0009-0004-8715-624X
Ailong KeDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA. ailong.ke@yale.edu.ORCID http://orcid.org/0000-0001-5957-7822
Weixin TangDepartment of Chemistry, The University of Chicago, Chicago, IL, USA. weixintang@uchicago.edu.ORCID http://orcid.org/0000-0002-5739-5416

Funding

Mechanistic Investigation of RNA-Mediated Gene Regulation and ImmunityR35GM118174 · NIGMS · YALE UNIVERSITY · PI AILONG KE · 2016 to 2026
$7.9M
American Cancer Society (American Cancer Society, Inc.) RSG-22-043-01-ETDavid and Lucile Packard Foundation (David & Lucile Packard Foundation) 2022-74685NIGMS NIH HHS R35 GM118174U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) GM118174
6 · The paper itself

Abstract

OMEGA RNA (ωRNA)-guided endonuclease IscB, the evolutionary ancestor of Cas9, is an attractive system for in vivo genome editing because of its compact size and mechanistic resemblance to Cas9. However, wild-type IscB-ωRNA systems show limited activity in human cells. Here we report enhanced OgeuIscB, which, with eight amino acid substitutions, displayed a fourfold increase in in vitro DNA-binding affinity and a 30.4-fold improvement in insertion-deletion (indel) formation efficiency in human cells. Paired with structure-guided ωRNA engineering, the enhanced OgeuIscB-ωRNA systems efficiently edited the human genome across 26 target sites, attaining up to 87.3% indel and 62.2% base-editing frequencies. Both wild-type and engineered OgeuIscB-ωRNA showed moderate fidelity in editing the human genome, with off-target profiles revealing key determinants of target selection including an NARR target-adjacent motif (TAM) and the TAM-proximal 14 nucleotides in the R-loop. Collectively, our engineered OgeuIscB-ωRNA systems are programmable, potent and sufficiently specific for human genome editing.

Indexed as

Gene EditingBacterial ProteinsCRISPR-Cas SystemsDNAEndonucleasesGenetic EngineeringGenome, HumanHEK293 CellsHumansINDEL MutationRNARNA, Guide, CRISPR-Cas SystemsBacterial ProteinsDNAEndonucleasesRNARNA, Guide, CRISPR-Cas Systems

Identifiers

PMID38977787
PMCPMC12213078

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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.