Evidence map›Paper›PMID 39939583›Full record

ArticleNature communications2025

EXPERT expands prime editing efficiency and range of large fragment edits.

Youcai Xiong, Yinyu Su, Ruigao He, Xiaosong Han, Sheng Li, Minghuan Liu, Xiaoning Xi, Zijia Liu, Heng Wang, Shengsong Xie and 7 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

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

  1. Pooled it
  2. Article
  3. 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
  4. Review
  5. Review
  6. Review
  7. Prime editing in mammals: From promise to practicalities.Molecular therapy. Nucleic acids · 2025
    Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. 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

17 authors.

Youcai Xiong *Frontiers Science Center for Animal Breeding and Sustainable Production, Huazhong Agricultural University, Wuhan, PR China.
Yinyu Su *Frontiers Science Center for Animal Breeding and Sustainable Production, Huazhong Agricultural University, Wuhan, PR China.
Ruigao He *Frontiers Science Center for Animal Breeding and Sustainable Production, Huazhong Agricultural University, Wuhan, PR China.
Xiaosong HanFrontiers Science Center for Animal Breeding and Sustainable Production, Huazhong Agricultural University, Wuhan, PR China.
Sheng LiFrontiers Science Center for Animal Breeding and Sustainable Production, Huazhong Agricultural University, Wuhan, PR China.
Minghuan LiuFrontiers Science Center for Animal Breeding and Sustainable Production, Huazhong Agricultural University, Wuhan, PR China.
Xiaoning XiFrontiers Science Center for Animal Breeding and Sustainable Production, Huazhong Agricultural University, Wuhan, PR China.
Zijia LiuFrontiers Science Center for Animal Breeding and Sustainable Production, Huazhong Agricultural University, Wuhan, PR China.
Heng WangFrontiers Science Center for Animal Breeding and Sustainable Production, Huazhong Agricultural University, Wuhan, PR China.ORCID http://orcid.org/0000-0002-1727-9226
Shengsong XieFrontiers Science Center for Animal Breeding and Sustainable Production, Huazhong Agricultural University, Wuhan, PR China.ORCID http://orcid.org/0000-0002-8301-877X
Xuewen XuFrontiers Science Center for Animal Breeding and Sustainable Production, Huazhong Agricultural University, Wuhan, PR China.
Kui LiAgricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, PR China.ORCID http://orcid.org/0000-0002-5686-3898
Jifeng ZhangCenter for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0001-5161-4705
Jie XuCenter for Advanced Models for Translational Sciences and Therapeutics, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID http://orcid.org/0000-0001-9452-2878
Xinyun LiFrontiers Science Center for Animal Breeding and Sustainable Production, Huazhong Agricultural University, Wuhan, PR China. xyli@mail.hzau.edu.cn.ORCID http://orcid.org/0000-0002-7943-1713
Shuhong ZhaoFrontiers Science Center for Animal Breeding and Sustainable Production, Huazhong Agricultural University, Wuhan, PR China. shzhao@mail.hzau.edu.cn.ORCID http://orcid.org/0000-0002-3997-2320
Jinxue RuanFrontiers Science Center for Animal Breeding and Sustainable Production, Huazhong Agricultural University, Wuhan, PR China. ruanjinxue@mail.hzau.edu.cn.ORCID http://orcid.org/0000-0002-0058-6924

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Prime editing systems (PEs) hold great promise in modern biotechnology. However, their editing range is limited as PEs can only modify the downstream sequences of the pegRNA nick. Here, we report the development of the extended prime editor system (EXPERT) to overcome this limitation by using an extended pegRNA (ext-pegRNA) with modified 3' extension, and an additional sgRNA (ups-sgRNA) targeting the upstream region of the ext-pegRNA. We demonstrate that EXPERT can efficiently perform editing on both sides of the ext-pegRNA nick, a task that is unattainable by canonical PEs. EXPERT exhibits prominent capacity in replacing sequences up to 88 base pairs and inserting sequences up to 100 base pairs within the upstream region of the ext-pegRNA nick. Compared to canonical PEs such as PE2, the utilization of the EXPERT strategy significantly enhances the editing efficiency for large fragment edits with an average improvement of 3.12-fold, up to 122.1 times higher. Safety wise, the use of ups-sgRNA does not increase the rates of undesirable insertions and deletions (indels), as the two nicks are on the same strand. Moreover, we do not observe increased off-target editing rates genome-wide. Our work introduces EXPERT as a PE tool with significant potential in life sciences.

Indexed as

CRISPR-Cas SystemsGene EditingHEK293 CellsHumansINDEL MutationRNA, Guide, CRISPR-Cas SystemsRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID39939583
PMCPMC11822059

What OpenQuestion holds

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LicenceCC BY
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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.