Evidence map›Paper›PMID 38956324›Full record

ArticleNature biotechnology2025

Tracking-seq reveals the heterogeneity of off-target effects in CRISPR-Cas9-mediated genome editing.

Ming Zhu, Runda Xu, Junsong Yuan, Jiacheng Wang, Xiaoyu Ren, Tingting Cong, Yaxian You, Anji Ju, Longchen Xu, Huimin Wang and 9 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing 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

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

  1. Pooled it
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  7. Precision modification of heart failure signaling by CRISPR-Cas9 base editing.Journal of molecular and cellular cardiology · 2026
    Review
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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

19 authors.

Ming Zhu *Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, China. zhu-m16@tsinghua.org.cn.ORCID http://orcid.org/0009-0003-6466-9686
Runda Xu *Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, China.ORCID http://orcid.org/0000-0002-2062-844X
Junsong Yuan *Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, China.
Jiacheng Wang *Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, China.
Xiaoyu RenTsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, China.
Tingting CongTsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, China.
Yaxian YouTsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, China.
Anji JuTsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, China.
Longchen XuTsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, China.
Huimin WangTsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, China.
Peiyuan ZhengTsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, China.
Huiying TaoDepartment of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
Chunhua LinDepartment of Urology, Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China.
Honghao YuDepartment of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China.
Juanjuan DuTsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, China.ORCID http://orcid.org/0000-0003-2151-4230
Xin LinTsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, China.ORCID http://orcid.org/0000-0003-0956-3654
Wei XieTsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, China.ORCID http://orcid.org/0000-0003-2126-3849
Yinqing LiMOE Key Laboratory of Bioinformatics, State Key Laboratory of Molecular Oncology, Tsinghua University, Beijing, China. yinqingl@tsinghua.edu.cn.ORCID http://orcid.org/0000-0002-9096-8482
Xun LanTsinghua-Peking Joint Center for Life Sciences, Tsinghua University, Beijing, China. xlan@mail.tsinghua.edu.cn.ORCID http://orcid.org/0000-0002-6523-046X

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32171448National Natural Science Foundation of China (National Science Foundation of China) 81972680
6 · The paper itself

Abstract

The continued development of novel genome editors calls for a universal method to analyze their off-target effects. Here we describe a versatile method, called Tracking-seq, for in situ identification of off-target effects that is broadly applicable to common genome-editing tools, including Cas9, base editors and prime editors. Through tracking replication protein A (RPA)-bound single-stranded DNA followed by strand-specific library construction, Tracking-seq requires a low cell input and is suitable for in vitro, ex vivo and in vivo genome editing, providing a sensitive and practical genome-wide approach for off-target detection in various scenarios. We show, using the same guide RNA, that Tracking-seq detects heterogeneity in off-target effects between different editor modalities and between different cell types, underscoring the necessity of direct measurement in the original system.

Indexed as

CRISPR-Cas SystemsGene EditingHumansRNA, Guide, CRISPR-Cas SystemsRNA, Guide, CRISPR-Cas Systems

Identifiers

What OpenQuestion holds

Textmetadata
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.