Evidence map›Paper›PMID 42328791›Full record

ArticleNucleic acids research2026

Prime editing-mediated microhomology enables efficient replacement of large DNA.

Yuyang Xie, Pan Li, Zhiyong He, Honglin Huang, Dingzhou Wu, Zhao Ma, Shenjiong Feng, Jiadong Ran, Kaixuan Hou, Fei Gao and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nucleic acids research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

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

  1. Pooled it
  2. Article
  3. 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

13 authors.

Yuyang XieFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
Pan LiXianghu Laboratory, Hangzhou 311231, China.
Zhiyong HeFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
Honglin HuangFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
Dingzhou WuFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
Zhao MaFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
Shenjiong FengFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
Jiadong RanFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
Kaixuan HouFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
Fei GaoFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
Xuguang DuFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
Mario R CapecchiDepartment of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT 84112, United States.
Sen WuFrontiers Science Center for Molecular Design Breeding (MOE), State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing 100193, China.ORCID 0000-0003-0764-6122

Funding

Biological Breeding - National Science and Technology Major Project 2024ZD04077China Agricultural UniversityChinese Universities Scientific Fund 2024TC167National Key Research and Development Program of China 2023YFC3402004National Key Research and Development Program of China 2023YFF1000204
6 · The paper itself

Abstract

Precise and efficient replacement of large genomic DNA segments without inducing double-strand breaks (DSBs) remains a central challenge in genome engineering. Traditional homologous recombination relies on DSBs and long homologous arms, yet it remains inefficient, while recombinase or integrase systems suffer from residual sequences at integration sites. Prime editing (PE), limited by the processivity of reverse transcriptase, struggles to integrate large fragments (>100 bp). To address this challenge, we introduce Prime Editing-Microhomology-Enabled Replacement (PREMIER), a DSB-free platform by installing single-stranded microhomology arms at donor and genomic junctions via PE. In cell lines, PREMIER achieved a mean efficiency of 63.4% (median 65.2%) in diverse target sites, with peak efficiencies reaching 85.9%, exceeding homology-directed repair by 10-20-fold and reducing off-target integrations by over 100-fold compared to nonhomologous end joining. It bypasses the need for long homology arms, simplifies donor preparation, achieves targeted replacement of sequences up to 10.3 kb. In vivo, PREMIER integrates a 6.2-kb oncogene cassette into the mouse liver. Additionally, PREMIER replaces murine Trp53 with human TP53 CDS, generating functional humanized mice. Altogether, PREMIER provides a precise, high-efficiency, and DSB-free strategy for large-scale genome rewriting, offering a powerful tool for complex modeling and therapeutic genome editing.

Indexed as

DNAGenetic EngineeringRecombinational DNA RepairAnimalsCell LineDNA Breaks, Double-StrandedHumansMiceTumor Suppressor Protein p53DNATumor Suppressor Protein p53

Identifiers

PMID42328791
PMCPMC13284714

What OpenQuestion holds

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LicenceCC BY
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.