Evidence map›Paper›PMID 29809142›Full record

ArticleeLife2018

Covalent linkage of the DNA repair template to the CRISPR-Cas9 nuclease enhances homology-directed repair.

Natasa Savic, Femke Cas Ringnalda, Helen Lindsay, Christian Berk, Katja Bargsten, Yizhou Li, Dario Neri, Mark D Robinson, Constance Ciaudo, Jonathan Hall and 2 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.

0numbers the graph read from it
0cells of the map it votes in
96citing papers in PubMed
7.9field-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

96 citing papers in PubMed, 165 citations in OpenAlex.

  1. Article
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  9. Precision T cell correction platform for inborn errors of immunity.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
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  19. A comprehensive review onFrontiers in genetics · 2024
    Review
  20. Review

36 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

12 authors at 3 institutions in 1 country.

Natasa Savic *The Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.ORCID https://orcid.org/0000-0003-3110-5780
Femke Cas Ringnalda *The Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-0684-4613
Helen LindsayThe Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
Christian BerkInstitute for Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
Katja BargstenDepartment of Biochemistry, University of Zurich, Zurich, Switzerland.
Yizhou LiInstitute for Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
Dario NeriInstitute for Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
Mark D RobinsonThe Institute of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.
Constance CiaudoThe Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-0857-4506
Jonathan HallInstitute for Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0003-4160-7135
Martin JinekDepartment of Biochemistry, University of Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0002-7601-210X
Gerald SchwankThe Institute of Molecular Health Sciences, ETH Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0003-0767-2953
ETH Zurich · CHSIB Swiss Institute of Bioinformatics · CHUniversity of Zurich · CH

Funding

Swiss National Science Foundation 31003A_149393Swiss National Science Foundation 31003A_160230Swiss National Science Foundation PMPDP3_171388
6 · The paper itself

Abstract

The CRISPR-Cas9 targeted nuclease technology allows the insertion of genetic modifications with single base-pair precision. The preference of mammalian cells to repair Cas9-induced DNA double-strand breaks via error-prone end-joining pathways rather than via homology-directed repair mechanisms, however, leads to relatively low rates of precise editing from donor DNA. Here we show that spatial and temporal co-localization of the donor template and Cas9 via covalent linkage increases the correction rates up to 24-fold, and demonstrate that the effect is mainly caused by an increase of donor template concentration in the nucleus. Enhanced correction rates were observed in multiple cell types and on different genomic loci, suggesting that covalently linking the donor template to the Cas9 complex provides advantages for clinical applications where high-fidelity repair is desired.

Indexed as

CRISPR-Cas SystemsDNA End-Joining RepairRecombinational DNA RepairCell NucleusClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated Protein 9DNADNA Breaks, Double-StrandedDNA ReplicationGene EditingGenetic LociGuanidinesHEK293 CellsHumansOligodeoxyribonucleotidesRecombinant Fusion ProteinsbenzylguanidineCRISPR-Associated Protein 9DNAGuanidinesOligodeoxyribonucleotidesRecombinant Fusion ProteinsRNA, Guide, CRISPR-Cas SystemschromosomesCRISPR/Cas9gene editinggene expressionhomology-directed repairhumanhuman biologymedicinemouse

Identifiers

PMID29809142
PMCPMC6023611
OpenAlexW2767634557

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.