Evidence map›Paper›PMID 40051369›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Enhancing Prime Editing Efficiency Through Modulation of Methylation on the Newly Synthesized DNA Strand and Prolonged Expression.

Xiaosong Han, Xianghua Xu, Youcai Xiong, Guangxing Zhao, Ruigao He, Yinyu Su, Sheng Li, Changzhi Zhao, Xiaoning Xi, Yunxia Zhao and 6 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

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

  1. Pooled it
  2. Article
  3. Review
  4. Article
  5. Article
  6. 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

16 authors.

Xiaosong HanKey Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, P. R. China.
Xianghua XuKey Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, P. R. China.
Youcai XiongKey Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, P. R. China.
Guangxing ZhaoKey Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, P. R. China.
Ruigao HeKey Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, P. R. China.
Yinyu SuKey Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, P. R. China.
Sheng LiKey Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, P. R. China.
Changzhi ZhaoKey Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, P. R. China.
Xiaoning XiKey Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, P. R. China.
Yunxia ZhaoKey Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, P. R. China.
Xuewen XuKey Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, P. R. China.
Shengsong XieKey Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, P. R. China.
Heng WangKey Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, P. R. China.
Xinyun LiKey Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, P. R. China.
Shuhong ZhaoKey Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, P. R. China.
Jinxue RuanKey Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education & Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture and Rural Affairs, Huazhong Agricultural University, Wuhan, 430070, P. R. China.ORCID https://orcid.org/0000-0002-0058-6924

Funding

China Postdoctoral Science Foundation 2021M690064China Postdoctoral Science Foundation 2022M711271Foundation for innovative Research Groups of the National Natural Science Foundation of china 32221005Major Science and Technology Projects in Hubei Province 2020ABA016National Key R&D Program of China 2021YFA0805903-3Natural Science Foundation of Hubei Province 2020CFA006STI2030-Major Projects 2023ZD0404703Wuhan Science and Technology 2022021302024853
6 · The paper itself

Abstract

Prime editors (PEs) have emerged as transformative tools for precision genome engineering, yet their broader application remains constrained by incomplete understanding of repair mechanisms. In this study, it is found that an increase in the methylation level of the CpG sequence on the newly generated strand can increase PE efficiency and that de novo DNA methyltransferases (DNMT3A/3B) are involved in the PE repair pathway. On the basis of these novel findings, the development of an episomal element-driven PE system (epiPE) achieved through the use of EBNA1/oriP are presented, which increases methylation levels around target sites and prolongs PE expression. A comparative analysis with canonical PE systems, including PE2, lentiPE2, and PE4max, reveals that the epiPE2 system significantly enhances editing efficiency while maintaining minimal insertion and deletion (indels) rates. Specifically, comparing to PE2, the epiPE2 system demonstrated an efficiency enhancement of 2.0 to 38.2-fold. In addition, the epiPE2 system is capable of efficient multiplex precise gene editing at up to 10 genetic loci in human cells. In conclusion, this findings increase the understanding of the PE repair mechanism, and presents the epiPE2 system as an efficient and multiplex-capable prime editing tool with potential applications in both basic research and translational studies.

Indexed as

DNADNA MethylationGene EditingHumansDNAEBNA1/oriPgene editingmethylationmultiplexprime editor

Identifiers

PMID40051369
PMCPMC12061241

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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.