Evidence map›Paper›PMID 38553609›Full record

ArticleNature chemical biology2024

Engineering APOBEC3A deaminase for highly accurate and efficient base editing.

Lei Yang, Yanan Huo, Man Wang, Dan Zhang, Tianai Zhang, Hao Wu, Xichen Rao, Haowei Meng, Shuming Yin, Jiale Mei and 13 more

Abstract read
PubMed Publisher
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 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
5.8field-weighted citation impact, top 3% 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

25 citing papers in PubMed, 25 citations in OpenAlex.

  1. Engineered Transformer Base Editor with Enhanced Editing Efficiency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
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  7. Efficient and Safe Knockout ofVeterinary sciences · 2026
    Article
  8. Article
  9. Review
  10. Article
  11. Article
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  13. Article
  14. Article
  15. Molecular therapy. Nucleic acids · 2025
    Review
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  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

23 authors at 4 institutions in 2 countries.

Lei Yang *Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Yanan Huo *Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Man Wang *Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Dan Zhang *Shanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Tianai ZhangShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Hao WuPeking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
Xichen RaoPeking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.ORCID http://orcid.org/0000-0003-2450-4521
Haowei MengPeking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.ORCID http://orcid.org/0000-0001-9695-5060
Shuming YinShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Jiale MeiShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Dexin ZhangXinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xi ChenBRL Medicine Inc., Shanghai, China.
Jia LvShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Meizhen LiuShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Yiyun ChengShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Yuting GuanShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.ORCID http://orcid.org/0000-0003-1866-270X
Bo FengSchool of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.ORCID http://orcid.org/0000-0002-4018-3257
Gaojie SongShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.ORCID http://orcid.org/0000-0002-7787-6452
Chengqi YiPeking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.ORCID http://orcid.org/0000-0003-2540-9729
Mingyao LiuShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.ORCID http://orcid.org/0000-0001-7339-5048
Fanyi ZengDepartment of Histo-Embryology, Genetics and Developmental Biology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. fzeng@vip.163.com.ORCID http://orcid.org/0000-0003-0955-5099
Liren WangShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. lrwang@bio.ecnu.edu.cn.ORCID http://orcid.org/0000-0001-5264-0921
Dali LiShanghai Frontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. dlli@bio.ecnu.edu.cn.ORCID http://orcid.org/0000-0002-0046-8493
East China Normal University · CNPeking University · CNShanghai Jiao Tong University · CNChinese University of Hong Kong · HK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cytosine base editors (CBEs) are effective tools for introducing C-to-T base conversions, but their clinical applications are limited by off-target and bystander effects. Through structure-guided engineering of human APOBEC3A (A3A) deaminase, we developed highly accurate A3A-CBE (haA3A-CBE) variants that efficiently generate C-to-T conversion with a narrow editing window and near-background level of DNA and RNA off-target activity, irrespective of methylation status and sequence context. The engineered deaminase domains are compatible with PAM-relaxed SpCas9-NG variant, enabling accurate correction of pathogenic mutations in homopolymeric cytosine sites through flexible positioning of the single-guide RNAs. Dual adeno-associated virus delivery of one haA3A-CBE variant to a mouse model of tyrosinemia induced up to 58.1% editing in liver tissues with minimal bystander editing, which was further reduced through single dose of lipid nanoparticle-based messenger RNA delivery of haA3A-CBEs. These results highlight the tremendous promise of haA3A-CBEs for precise genome editing to treat human diseases.

Indexed as

Cytidine DeaminaseGene EditingAnimalsCRISPR-Cas SystemsCytosineDependovirusHEK293 CellsHumansMiceProtein EngineeringProteinsAPOBEC3A protein, humanCytidine DeaminaseCytosineProteins

Identifiers

PMID38553609
OpenAlexW4393317467

What OpenQuestion holds

Textmetadata
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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.