Evidence map›Paper›PMID 35831290›Full record

ArticleNature communications2022

Massively targeted evaluation of therapeutic CRISPR off-targets in cells.

Xiaoguang Pan, Kunli Qu, Hao Yuan, Xi Xiang, Christian Anthon, Liubov Pashkova, Xue Liang, Peng Han, Giulia I Corsi, Fengping Xu and 15 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 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.0field-weighted citation impact, top 7% 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

28 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
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  4. Medea: An omics AI agent for therapeutic discovery.bioRxiv : the preprint server for biology · 2026
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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

25 authors at 6 institutions in 3 countries.

Xiaoguang Pan *Lars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, BGI-Shenzhen, Qingdao, China.
Kunli Qu *Lars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, BGI-Shenzhen, Qingdao, China.
Hao Yuan *Lars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, BGI-Shenzhen, Qingdao, China.
Xi Xiang *Lars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, BGI-Shenzhen, Qingdao, China.
Christian Anthon *Center for non-coding RNA in Technology and Health, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.ORCID 0000-0002-4336-1688
Liubov PashkovaCenter for non-coding RNA in Technology and Health, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.ORCID 0000-0002-7195-9329
Xue LiangLars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, BGI-Shenzhen, Qingdao, China.
Peng HanLars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, BGI-Shenzhen, Qingdao, China.ORCID 0000-0002-3405-087X
Giulia I CorsiCenter for non-coding RNA in Technology and Health, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark.ORCID 0000-0001-5932-0664
Fengping XuLars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, BGI-Shenzhen, Qingdao, China.
Ping LiuBGI-Research, BGI-Shenzhen, Shenzhen, China.
Jiayan ZhongBGI-Research, BGI-Shenzhen, Shenzhen, China.
Yan ZhouDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.
Tao MaBGI-Research, BGI-Shenzhen, Shenzhen, China.
Hui JiangBGI-Research, BGI-Shenzhen, Shenzhen, China.
Junnian LiuLars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, BGI-Shenzhen, Qingdao, China.
Jian WangBGI-Research, BGI-Shenzhen, Shenzhen, China.
Niels JessenDepartment of Biomedicine, Aarhus University, Aarhus, Denmark.ORCID 0000-0001-5613-7274
Lars BolundLars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, BGI-Shenzhen, Qingdao, China.
Huanming YangBGI-Research, BGI-Shenzhen, Shenzhen, China.
Xun XuBGI-Research, BGI-Shenzhen, Shenzhen, China.ORCID 0000-0002-5338-5173
George M ChurchDepartment of Genetics, Blavatnik Institute, Harvard Medical School, Boston, MA, USA. gchurch@genetics.med.harvard.edu.
Jan GorodkinCenter for non-coding RNA in Technology and Health, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg, Denmark. gorodkin@rth.dk.ORCID 0000-0001-5823-4000
Lin LinDepartment of Biomedicine, Aarhus University, Aarhus, Denmark. lin.lin@biomed.au.dk.ORCID 0000-0002-7546-4948
Yonglun LuoLars Bolund Institute of Regenerative Medicine, Qingdao-Europe Advanced Institute for Life Sciences, BGI-Qingdao, BGI-Shenzhen, Qingdao, China. alun@biomed.au.dk.ORCID 0000-0002-0007-7759
BGI Group (China) · CNUniversity of Copenhagen · DKAarhus University · DKSteno Diabetes Centers · DKHarvard University · USUniversity of Chinese Academy of Sciences · CN

Funding

Center for Genomically Engineered OrgansRM1HG008525 · NHGRI · HARVARD MEDICAL SCHOOL · PI CHURCH, GEORGE M · 2015 to 2019
$10.2M
NHGRI NIH HHS RM1 HG008525
6 · The paper itself

Abstract

Methods for sensitive and high-throughput evaluation of CRISPR RNA-guided nucleases (RGNs) off-targets (OTs) are essential for advancing RGN-based gene therapies. Here we report SURRO-seq for simultaneously evaluating thousands of therapeutic RGN OTs in cells. SURRO-seq captures RGN-induced indels in cells by pooled lentiviral OTs libraries and deep sequencing, an approach comparable and complementary to OTs detection by T7 endonuclease 1, GUIDE-seq, and CIRCLE-seq. Application of SURRO-seq to 8150 OTs from 110 therapeutic RGNs identifies significantly detectable indels in 783 OTs, of which 37 OTs are found in cancer genes and 23 OTs are further validated in five human cell lines by targeted amplicon sequencing. Finally, SURRO-seq reveals that thermodynamically stable wobble base pair (rG•dT) and free binding energy strongly affect RGN specificity. Our study emphasizes the necessity of thoroughly evaluating therapeutic RGN OTs to minimize inevitable off-target effects.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsRNA, Guide, CRISPR-Cas SystemsCell LineCRISPR-Cas SystemsEndonucleasesHigh-Throughput Nucleotide SequencingHumansRibonucleasesEndonucleasesRibonucleasesRNA, Guide, CRISPR-Cas Systems

Identifiers

PMID35831290
PMCPMC9279339
OpenAlexW4285088294

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.