Evidence map›Paper›PMID 36658146›Full record

ArticleNature communications2023

Development of a versatile nuclease prime editor with upgraded precision.

Xiangyang Li, Guiquan Zhang, Shisheng Huang, Yao Liu, Jin Tang, Mingtian Zhong, Xin Wang, Wenjun Sun, Yuan Yao, Quanjiang Ji and 4 more

Abstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
–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

23 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. A primer on prime: A prime editing update from advances to first-in-human trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Review
  6. Review
  7. Article
  8. Animals : an open access journal from MDPI · 2025
    Review
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  14. Review
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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

14 authors.

Xiangyang Li *Gene Editing Center, School of Life Science and Technology, ShanghaiTech University, 100 Haike Rd., Pudong New Area, Shanghai, 201210, China.
Guiquan Zhang *Zhejiang Lab, Hangzhou, Zhejiang, 311121, China.
Shisheng Huang *Zhejiang Lab, Hangzhou, Zhejiang, 311121, China.
Yao LiuKey Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, 712100, Yangling, Shaanxi, China.
Jin TangZhejiang Lab, Hangzhou, Zhejiang, 311121, China.
Mingtian ZhongInstitute for Brain Research and Rehabilitation, South China Normal University, Guangzhou, 510631, China.
Xin WangGene Editing Center, School of Life Science and Technology, ShanghaiTech University, 100 Haike Rd., Pudong New Area, Shanghai, 201210, China.
Wenjun SunGene Editing Center, School of Life Science and Technology, ShanghaiTech University, 100 Haike Rd., Pudong New Area, Shanghai, 201210, China.
Yuan YaoZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, 311215, China.
Quanjiang JiSchool of Physical Science and Technology, ShanghaiTech University, 100 Haike Rd., Pudong New Area, Shanghai, 201210, China.ORCID 0000-0002-2321-8462
Xiaolong WangKey Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, 712100, Yangling, Shaanxi, China.ORCID 0000-0003-1620-1344
Jianghuai LiuState Key Laboratory of Pharmaceutical Biotechnology, Model Animal Research Center at Medical School of Nanjing University, 210061, Nanjing, China. liujianghuai@nju.edu.cn.ORCID 0000-0002-2382-9140
Shiqiang ZhuZhejiang Lab, Hangzhou, Zhejiang, 311121, China. zhusq@zhejianglab.com.
Xingxu HuangGene Editing Center, School of Life Science and Technology, ShanghaiTech University, 100 Haike Rd., Pudong New Area, Shanghai, 201210, China. huangxx@shanghaitech.edu.cn.ORCID 0000-0001-8934-1247

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The applicability of nuclease-based form of prime editor (PEn) has been hindered by its complexed editing outcomes. A chemical inhibitor against DNA-PK, which mediates the nonhomologous end joining (NHEJ) pathway, was recently shown to promote precise insertions by PEn. Nevertheless, the intrinsic issues of specificity and toxicity for such a chemical approach necessitate development of alternative strategies. Here, we find that co-introduction of PEn and a NHEJ-restraining, 53BP1-inhibitory ubiquitin variant potently drives precise edits via mitigation of unintended edits, framing a high-activity editing platform (uPEn) apparently complementing the canonical PE. Further developments involve exploring the effective configuration of a homologous region-containing pegRNA (HR-pegRNA). Overall, uPEn can empower high-efficiency installation of insertions (38%), deletions (43%) and replacements (52%) in HEK293T cells. When compared with PE3/5max, uPEn demonstrates superior activities for typically refractory base substitutions, and for small-block edits. Collectively, this work establishes a highly efficient PE platform with broad application potential.

Indexed as

DNA Breaks, Double-StrandedGene EditingCRISPR-Cas SystemsDNA End-Joining RepairHEK293 CellsHumans

Identifiers

PMID36658146
PMCPMC9852468

What OpenQuestion holds

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LicenceCC BY
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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.