Evidence map›Paper›PMID 39747083›Full record

ArticleNature communications2025

Mismatch prime editing gRNA increased efficiency and reduced indels.

Jidong Fei, Dongdong Zhao, Caiyi Pang, Ju Li, Siwei Li, Wentao Qiao, Juan Tan, Changhao Bi, Xueli Zhang

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. Prime Editing: An Overview.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Gene Editing inJournal of fungi (Basel, Switzerland) · 2025
    Review
  12. Elf1 Deficiency Impairs Macrophage Development in Zebrafish Model Organism.International journal of molecular sciences · 2025
    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.

Jidong Fei *College of Life Science, Tianjin Normal University, Tianjin, China.
Dongdong Zhao *Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China. zhao_dd@tib.cas.cn.ORCID 0000-0001-9691-1308
Caiyi Pang *Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.
Ju Li *College of Life Science, Tianjin Normal University, Tianjin, China.ORCID 0000-0003-0037-4144
Siwei LiTianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China.ORCID 0000-0001-6057-2957
Wentao QiaoKey Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
Juan TanKey Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China.
Changhao BiTianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China. bi_ch@tib.cas.cn.ORCID 0000-0002-1940-8511
Xueli ZhangTianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, China. zhang_xl@tib.cas.cn.ORCID 0000-0002-8660-4037

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32171449National Natural Science Foundation of China (National Science Foundation of China) 32225031National Natural Science Foundation of China (National Science Foundation of China) 32271483Youth Innovation Promotion Association of the Chinese Academy of Sciences (Youth Innovation Promotion Association CAS) 2022177
6 · The paper itself

Abstract

Prime editing enables precise and efficient genome editing, but its efficacy is hindered by pegRNA's 3' extension, forming secondary structures due to high complementarity with the protospacer. The continuous presence of the prime editing system also leads to unintended indel formation, raising safety concerns for therapeutic applications. To address these challenges, we develop a mismatched pegRNA (mpegRNA) strategy that introduces mismatched bases into the pegRNA protospacer, reducing complementarity and secondary structure formation, and preventing sustained activity. Our findings show that mpegRNA enhances editing efficiency by up to 2.3 times and reduces indel levels by 76.5% without compromising performance. Combining mpegRNA with epegRNA further increases efficiency up to 14-fold, or 2.4-fold in PE4max/PE5max systems, underscoring its potential in research and therapy. AlphaFold 3 analysis suggests that the optimal mpegRNA structure contributes significantly to improved editing outcomes. Overall, mpegRNA advances prime editing technology, improving efficiency while reducing indels.

Indexed as

CRISPR-Cas SystemsGene EditingINDEL MutationRNA, Guide, CRISPR-Cas SystemsBase Pair MismatchHEK293 CellsHumansRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID39747083
PMCPMC11696010

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

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.