Evidence map›Paper›PMID 39284833›Full record

ArticleNature communications2024

Engineering TadA ortholog-derived cytosine base editor without motif preference and adenosine activity limitation.

Guoling Li, Xue Dong, Jiamin Luo, Tanglong Yuan, Tong Li, Guoli Zhao, Hainan Zhang, Jingxing Zhou, Zhenhai Zeng, Shuna Cui and 8 more

Erratum issuedAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Molecular therapy. Nucleic acids · 2025
    Review
  6. Animals : an open access journal from MDPI · 2025
    Review
  7. Efforts to Downsize Base Editors for Clinical Applications.International journal of molecular sciences · 2025
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Guoling Li *HuidaGene Therapeutics Co., Ltd., Shanghai, 200131, China.ORCID 0000-0003-0422-6157
Xue Dong *HuidaGene Therapeutics Co., Ltd., Shanghai, 200131, China.
Jiamin Luo *HuidaGene Therapeutics Co., Ltd., Shanghai, 200131, China.
Tanglong Yuan *Shenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Key Laboratory of Synthetic Biology, Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.ORCID 0000-0003-4670-2625
Tong Li *HuidaGene Therapeutics Co., Ltd., Shanghai, 200131, China.ORCID 0009-0001-3934-9184
Guoli Zhao *Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University; NHC Key Laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, China.
Hainan ZhangHuidaGene Therapeutics Co., Ltd., Shanghai, 200131, China.
Jingxing ZhouHuidaGene Therapeutics Co., Ltd., Shanghai, 200131, China.
Zhenhai ZengEye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University; NHC Key Laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, China.
Shuna CuiHuidaGene Therapeutics Co., Ltd., Shanghai, 200131, China.
Haoqiang WangHuidaGene Therapeutics Co., Ltd., Shanghai, 200131, China.ORCID 0000-0003-4944-1117
Yin WangHuidaGene Therapeutics Co., Ltd., Shanghai, 200131, China.
Yuyang YuHuidaGene Therapeutics Co., Ltd., Shanghai, 200131, China.
Yuan YuanHuidaGene Therapeutics Co., Ltd., Shanghai, 200131, China.
Erwei ZuoShenzhen Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Key Laboratory of Synthetic Biology, Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China. zuoerwei@caas.cn.ORCID 0000-0001-8259-0275
Chunlong XuLingang Laboratory, Shanghai, China. xucl@lglab.ac.cn.ORCID 0000-0003-3533-3465
Jinhai HuangEye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University; NHC Key Laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, China. jinhaihuang@fudan.edu.cn.ORCID 0000-0001-9952-3175
Yingsi ZhouHuidaGene Therapeutics Co., Ltd., Shanghai, 200131, China. yingsizhou@huidagene.com.ORCID 0000-0002-6541-2116

Funding

National Natural Science Foundation of China (National Science Foundation of China) 82271048National Natural Science Foundation of China (National Science Foundation of China) 82301215Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission) 23XD1420500
6 · The paper itself

Abstract

The engineered TadA variants used in cytosine base editors (CBEs) present distinctive advantages, including a smaller size and fewer off-target effects compared to cytosine base editors that rely on natural deaminases. However, the current TadA variants demonstrate a preference for base editing in DNA with specific motif sequences and possess dual deaminase activity, acting on both cytosine and adenosine in adjacent positions, limiting their application scope. To address these issues, we employ TadA orthologs screening and multi sequence alignment (MSA)-guided protein engineering techniques to create a highly effective cytosine base editor (aTdCBE) without motif and adenosine deaminase activity limitations. Notably, the delivery of aTdCBE to a humanized mouse model of Duchenne muscular dystrophy (DMD) mice achieves robust exon 55 skipping and restoration of dystrophin expression. Our advancement in engineering TadA ortholog for cytosine editing enriches the base editing toolkits for gene-editing therapy and other potential applications.

Indexed as

AdenosineCytosineGene EditingMuscular Dystrophy, DuchenneAdenosine DeaminaseAnimalsCRISPR-Cas SystemsDisease Models, AnimalDystrophinEscherichia coli ProteinsExonsHEK293 CellsHumansMiceProtein EngineeringAdenosineAdenosine DeaminaseCytosineDystrophinEscherichia coli ProteinsTadA protein, E coli

Identifiers

PMID39284833
PMCPMC11405849

What OpenQuestion holds

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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.