Evidence map›Paper›PMID 40021632›Full record

ArticleNature communications2025

Improving adenine base editing precision by enlarging the recognition domain of CRISPR-Cas9.

Shuliang Gao, Benson Weng, Douglas Wich, Liam Power, Mengting Chen, Huiwen Guan, Zhongfeng Ye, Chutian Xu, Qiaobing Xu

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Advances in CRISPR-Cas for Diagnosis and Treatment ofPathogens (Basel, Switzerland) · 2026
    Review
  3. 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

9 authors.

Shuliang GaoDepartment of Biomedical Engineering, Tufts University, Medford, MA, USA.
Benson WengDepartment of Biomedical Engineering, Tufts University, Medford, MA, USA.
Douglas WichDepartment of Biomedical Engineering, Tufts University, Medford, MA, USA.
Liam PowerDepartment of Biomedical Engineering, Tufts University, Medford, MA, USA.ORCID http://orcid.org/0000-0002-3402-8429
Mengting ChenDepartment of Biomedical Engineering, Tufts University, Medford, MA, USA.
Huiwen GuanDepartment of Biomedical Engineering, Tufts University, Medford, MA, USA.
Zhongfeng YeDepartment of Biomedical Engineering, Tufts University, Medford, MA, USA.
Chutian XuDepartment of Biomedical Engineering, Tufts University, Medford, MA, USA.
Qiaobing XuDepartment of Biomedical Engineering, Tufts University, Medford, MA, USA. Qiaobing.Xu@tufts.edu.ORCID http://orcid.org/0000-0001-7323-7795

Funding

Efficient in Vivo RNP-based Gene Editing in the Sensory Organ Inner Ear Using Bioreducible Lipid NanoparticlesUG3TR002636 · NCATS · MASSACHUSETTS EYE AND EAR INFIRMARY · PI CHEN, ZHENG-YI, LIU, DAVID R · 2018 to 2020
$2.4M
NCATS NIH HHS UG3 TR002636
6 · The paper itself

Abstract

Domain expansion contributes to diversification of RNA-guided-endonucleases including Cas9. However, it remains unclear how REC domain expansion could benefit Cas9. In this study, we identify an insertion spot that is compatible with large REC insertion and succeeds in enlarging the non-catalytic REC domain of Streptococcus pyogenes Cas9. The natural-evolution-like giant SpCas9 (GS-Cas9) is created and shows substantially improved editing precision. We further discover that enlarging the REC domain could enable regulation of the N-terminal adenine deaminase TadA8e tethered to the Cas9 scaffold, which contributes to substantially reducing unexpected editing and improving the precision of the adenine base editor ABE8e. We provide proof of concept for evolution-inspired expansion of Cas9 and offer an alternative solution for optimizing gene editors. Our study also indicates a vast potential for engineering the topological malleability of RNA-guided endonucleases and base editors.

Indexed as

AdenineCRISPR-Associated Protein 9CRISPR-Cas SystemsGene EditingAminohydrolasesHEK293 CellsHumansProtein DomainsRNA, Guide, CRISPR-Cas SystemsStreptococcus pyogenesAdenineadenine deaminaseAminohydrolasesCRISPR-Associated Protein 9RNA, Guide, CRISPR-Cas Systems

Identifiers

PMID40021632
PMCPMC11871365

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.