Evidence map›Paper›PMID 33863894›Full record

ArticleNature communications2021

Structure-guided engineering of adenine base editor with minimized RNA off-targeting activity.

Jianan Li, Wenxia Yu, Shisheng Huang, Susu Wu, Liping Li, Jiankui Zhou, Yu Cao, Xingxu Huang, Yunbo Qiao

Abstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing 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

45 citing papers in PubMed.

  1. Base Editing: Mechanisms and Therapeutic Applications.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. miRNA modules for precise, tunable control of gene expression.bioRxiv : the preprint server for biology · 2025
    Article
  9. Review
  10. Article
  11. Review
  12. Review
  13. Advancing Precision Medicine: Recent Innovations in Gene Editing Technologies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Review
  14. Efforts to Downsize Base Editors for Clinical Applications.International journal of molecular sciences · 2025
    Review
  15. The lives of cells, recorded.Nature reviews. Genetics · 2025
    Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. 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.

Jianan Li *School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Wenxia Yu *School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Shisheng Huang *School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Susu WuPrecise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou, China.
Liping LiPrecise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou, China.
Jiankui ZhouPrecise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou, China.ORCID 0000-0002-7099-4528
Yu CaoDepartment of Orthopaedics and Institute of Precision Medicine, Shanghai Key Laboratory of Orthopaedic Implant Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.ORCID 0000-0003-1409-2068
Xingxu HuangSchool of Life Science and Technology, ShanghaiTech University, Shanghai, China. huangxx@shanghaitech.edu.cn.ORCID 0000-0001-8934-1247
Yunbo QiaoPrecise Genome Engineering Center, School of Life Sciences, Guangzhou University, Guangzhou, China. ybqiao@gzhu.edu.cn.ORCID 0000-0002-8391-5868

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Both adenine base editors (ABEs) and cytosine base editors (CBEs) have been recently revealed to induce transcriptome-wide RNA off-target editing in a guide RNA-independent manner. Here we construct a reporter system containing E.coli Hokb gene with a tRNA-like motif for robust detection of RNA editing activities as the optimized ABE, ABEmax, induces highly efficient A-to-I (inosine) editing within an E.coli tRNA-like structure. Then, we design mutations to disrupt the potential interaction between TadA and tRNAs in structure-guided principles and find that Arginine 153 (R153) within TadA is essential for deaminating RNAs with core tRNA-like structures. Two ABEmax or mini ABEmax variants (TadA* fused with Cas9n) with deletion of R153 within TadA and/or TadA* (named as del153/del153* and mini del153) are successfully engineered, showing minimized RNA off-targeting, but comparable DNA on-targeting activities. Moreover, R153 deletion in recently reported ABE8e or ABE8s can also largely reduce their RNA off-targeting activities. Taken together, we develop a strategy to generate engineered ABEs (eABEs) with minimized RNA off-targeting activities.

Indexed as

AdenineAdenosine DeaminaseBacterial ToxinsCell Line, TumorCRISPR-Associated Protein 9CytosineDNAEscherichia coli ProteinsGene EditingGenes, ReporterHEK293 CellsHumansInosineProtein EngineeringRecombinant Fusion ProteinsRNA EditingAdenineAdenosine DeaminaseBacterial ToxinsCRISPR-Associated Protein 9CytosineDNAEscherichia coli ProteinsHokB protein, E coliInosineRecombinant Fusion ProteinsRNA, TransferTadA protein, E coli

Identifiers

PMID33863894
PMCPMC8052359

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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.