Evidence map›Paper›PMID 33288953›Full record

ReviewNature protocols2021

Tools for experimental and computational analyses of off-target editing by programmable nucleases.

X Robert Bao, Yidan Pan, Ciaran M Lee, Timothy H Davis, Gang Bao

Open access · bronzeAbstract readReview
In one paragraph

Review in Nature protocols, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% 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

68 citing papers in PubMed, 1 synthesis or guideline pooled it, 95 citations in OpenAlex.

  1. Guideline
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  3. Review
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  6. Article
  7. Clinical translation of epigenome editing technologies.Current opinion in biomedical engineering · 2026
    Article
  8. Review
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  10. Article
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  14. Safety Aspects of Cell Culture-Derived Food for Human Consumption.Advances in biochemical engineering/biotechnology · 2026
    Review
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8 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

5 authors at 3 institutions in 2 countries.

X Robert Bao *ILISATech, Houston, TX, USA.
Yidan Pan *Department of Bioengineering, Rice University, Houston, TX, USA.ORCID http://orcid.org/0000-0002-9702-8530
Ciaran M Lee *APC Microbiome Ireland, University College Cork, Cork, Ireland.
Timothy H DavisDepartment of Bioengineering, Rice University, Houston, TX, USA.
Gang BaoDepartment of Bioengineering, Rice University, Houston, TX, USA. gang.bao@rice.edu.ORCID http://orcid.org/0000-0001-5501-554X
Rice University · USArsenal Biosciences (United States) · USUniversity College Cork · IE

Funding

HBB gene-editing for treating sickle cell diseaseR01HL152314 · NHLBI · RICE UNIVERSITY · PI BAO, GANG · 2020 to 2023
$2.5M
Velcro AAV Vector for tissue-specific delivery of genome editing reagents with enhanced cargo capacityUG3HL151545 · NHLBI · RICE UNIVERSITY · PI BAO, GANG, LAGOR, WILLIAM RAYMOND · 2019 to 2021
$2.3M
Addressing safety issues by quantify large deletions and chromosomal rearrangements in HBB gene editingOT2HL154977 · NHLBI · RICE UNIVERSITY · PI BAO, GANG · 2020 to 2020
$1.2M
NHLBI NIH HHS OT2 HL154977NHLBI NIH HHS R01 HL152314NHLBI NIH HHS UG3 HL151545
6 · The paper itself

Abstract

Genome editing using programmable nucleases is revolutionizing life science and medicine. Off-target editing by these nucleases remains a considerable concern, especially in therapeutic applications. Here we review tools developed for identifying potential off-target editing sites and compare the ability of these tools to properly analyze off-target effects. Recent advances in both in silico and experimental tools for off-target analysis have generated remarkably concordant results for sites with high off-target editing activity. However, no single tool is able to accurately predict low-frequency off-target editing, presenting a bottleneck in therapeutic genome editing, because even a small number of cells with off-target editing can be detrimental. Therefore, we recommend that at least one in silico tool and one experimental tool should be used together to identify potential off-target sites, and amplicon-based next-generation sequencing (NGS) should be used as the gold standard assay for assessing the true off-target effects at these candidate sites. Future work to improve off-target analysis includes expanding the true off-target editing dataset to evaluate new experimental techniques and to train machine learning algorithms; performing analysis using the particular genome of the cells in question rather than the reference genome; and applying novel NGS techniques to improve the sensitivity of amplicon-based off-target editing quantification.

Indexed as

CRISPR-Cas SystemsAnimalsEndonucleasesGene EditingGenomicsHigh-Throughput Nucleotide SequencingHumansEndonucleases

Identifiers

PMID33288953
PMCPMC8049448
OpenAlexW3111011311

What OpenQuestion holds

Textmetadata
LicenceTDM
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.