Evidence map›Paper›PMID 35351879›Full record

ArticleNature communications2022

Highly efficient prime editing by introducing same-sense mutations in pegRNA or stabilizing its structure.

Xiaosa Li, Lina Zhou, Bao-Qing Gao, Guangye Li, Xiao Wang, Ying Wang, Jia Wei, Wenyan Han, Zixian Wang, Jifang Li and 8 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed, 1 pooled it
10.9field-weighted citation impact, top 1% of its field
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

92 citing papers in PubMed, 1 synthesis or guideline pooled it, 132 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Article
  6. 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
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Gene-sized editing for the therapy of genetic diseases.Functional & integrative genomics · 2026
    Review
  13. Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Advancements in CRISPR-basedFrontiers in genome editing · 2026
    Review
  19. Article
  20. Review

32 more citing papers are in PubMed but not listed here.

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

18 authors at 5 institutions in 2 countries.

Xiaosa Li *Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 200080, Shanghai, China. xiaosa.li@shgh.cn.ORCID 0000-0002-0451-002X
Lina Zhou *Gene Editing Center, School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China.
Bao-Qing Gao *CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 200031, Shanghai, China.
Guangye LiGene Editing Center, School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China.
Xiao WangGene Editing Center, School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China.
Ying WangCAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 200031, Shanghai, China.
Jia WeiCAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 200031, Shanghai, China.
Wenyan HanGene Editing Center, School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China.
Zixian WangGene Editing Center, School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China.
Jifang LiGene Editing Center, School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China.
Runze GaoGene Editing Center, School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China.ORCID 0000-0002-2434-8576
Junjie ZhuGene Editing Center, School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China.
Wenchao XuGene Editing Center, School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China.
Jing WuGene Editing Center, School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China.
Bei YangShanghai Clinical Research and Trial Center, 201210, Shanghai, China.ORCID 0000-0001-5389-3859
Xiaodong SunDepartment of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 200080, Shanghai, China. xdsun@sjtu.edu.cn.ORCID 0000-0001-5015-0945
Li YangCenter for Molecular Medicine, Children's Hospital, Fudan University and Shanghai Key Laboratory of Medical Epigenetics, International Laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, Shanghai, 200032, China. liyang_fudan@fudan.edu.cn.ORCID 0000-0001-8833-7473
Jia ChenGene Editing Center, School of Life Science and Technology, ShanghaiTech University, 201210, Shanghai, China. chenjia@shanghaitech.edu.cn.ORCID 0000-0002-4242-2899
Chinese Academy of Sciences · CNShanghai Institute of Nutrition and Health · CNShanghaiTech University · CNShanghai Jiao Tong University · CNFudan University · CN

Funding

Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) 2018YFA0801401Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) 2018YFC1004602Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) 2018ZX10731-101-001-010Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology) 2019YFA0802804National Natural Science Foundation of China (National Science Foundation of China) 31822016National Natural Science Foundation of China (National Science Foundation of China) 31925011National Natural Science Foundation of China (National Science Foundation of China) 32070170National Natural Science Foundation of China (National Science Foundation of China) 91940306Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission) 21JC1404600
6 · The paper itself

Abstract

Prime editor (PE), which is developed by combining Cas9 nickase and an engineered reverse transcriptase, can mediate all twelve types of base substitutions and small insertions or deletions in living cells but its efficiency remains low. Here, we develop spegRNA by introducing same-sense mutations at proper positions in the reverse-transcription template of pegRNA to increase PE's base-editing efficiency up-to 4,976-fold (on-average 353-fold). We also develop apegRNA by altering the pegRNA secondary structure to increase PE's indel-editing efficiency up-to 10.6-fold (on-average 2.77-fold). The spegRNA and apegRNA can be combined to further enhance editing efficiency. When spegRNA and apegRNA are used in PE3 and PE5 systems, the efficiencies of sPE3, aPE3, sPE5 and aPE5 systems are all enhanced significantly. The strategies developed in this study realize highly efficient prime editing at certain previously uneditable sites.

Indexed as

CRISPR-Cas SystemsGene EditingINDEL MutationMutationRNA-Directed DNA PolymeraseRNA-Directed DNA Polymerase

Identifiers

PMID35351879
PMCPMC8964725
OpenAlexW4221033791

What OpenQuestion holds

Textmetadata
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.