Evidence map›Paper›PMID 33504770›Full record

ArticleNature communications2021

TALEN outperforms Cas9 in editing heterochromatin target sites.

Surbhi Jain, Saurabh Shukla, Che Yang, Meng Zhang, Zia Fatma, Manasi Lingamaneni, Shireen Abesteh, Stephan Thomas Lane, Xiong Xiong, Yuchuan Wang and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
6.2field-weighted citation impact, top 2% 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

55 citing papers in PubMed, 95 citations in OpenAlex.

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  14. Phosphatidylinositol-3-phosphate mediates Arc capsid secretion through the multivesicular body pathway.Proceedings of the National Academy of Sciences of the United States of America · 2024
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  15. Accelerating Diverse Cell-Based Therapies Through Scalable Design.Annual review of chemical and biomolecular engineering · 2024
    Review
  16. 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

13 authors at 2 institutions in 1 country.

Surbhi Jain *Department of Biochemistry, School of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Saurabh Shukla *Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.ORCID 0000-0002-7632-8163
Che YangDepartment of Biochemistry, School of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Meng ZhangDepartment of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.ORCID 0000-0002-4076-6276
Zia FatmaDepartment of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Manasi LingamaneniDepartment of Biochemistry, School of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Shireen AbestehDepartment of Biochemistry, School of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Stephan Thomas LaneCarl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Xiong XiongDepartment of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Yuchuan WangComputational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, 15213, USA.
Charles M SchroederDepartment of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Paul R SelvinCenter for the Physics of Living Cells, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA.
Huimin ZhaoDepartment of Biochemistry, School of Molecular and Cellular Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA. zhao5@illinois.edu.ORCID 0000-0002-9069-6739
University of Illinois Urbana-Champaign · USCarnegie Mellon University · US

Funding

Mapping Technology DevelopmentU54DK107965 · NIDDK · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI MA, JIAN · 2015 to 2019
$8.6M
High throughput CRISPR-mediated functional validation of regulatory elementsUM1HG009402 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI REN, BING, SHEN, YIN · 2017 to 2021
$8.4M
NHGRI NIH HHS UM1 HG009402NIDDK NIH HHS U54 DK107965
6 · The paper itself

Abstract

Genome editing critically relies on selective recognition of target sites. However, despite recent progress, the underlying search mechanism of genome-editing proteins is not fully understood in the context of cellular chromatin environments. Here, we use single-molecule imaging in live cells to directly study the behavior of CRISPR/Cas9 and TALEN. Our single-molecule imaging of genome-editing proteins reveals that Cas9 is less efficient in heterochromatin than TALEN because Cas9 becomes encumbered by local searches on non-specific sites in these regions. We find up to a fivefold increase in editing efficiency for TALEN compared to Cas9 in heterochromatin regions. Overall, our results show that Cas9 and TALEN use a combination of 3-D and local searches to identify target sites, and the nanoscopic granularity of local search determines the editing outcomes of the genome-editing proteins. Taken together, our results suggest that TALEN is a more efficient gene-editing tool than Cas9 for applications in heterochromatin.

Indexed as

Gene EditingCRISPR-Associated Protein 9DNA-Binding ProteinsHEK293 CellsHeLa CellsHeterochromatinHumansSingle Molecule ImagingTranscription Activator-Like Effector NucleasesCRISPR-Associated Protein 9DNA-Binding ProteinsHeterochromatinTranscription Activator-Like Effector Nucleases

Identifiers

PMID33504770
PMCPMC7840734
OpenAlexW3122643449

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.