Evidence map›Paper›PMID 39134754›Full record

ArticleNature biotechnology2025

Removal of TREX1 activity enhances CRISPR-Cas9-mediated homologous recombination.

Mehmet E Karasu, Eléonore Toufektchan, Yanyang Chen, Alessandra Albertelli, Grégoire Cullot, John Maciejowski, Jacob E Corn

Abstract read
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 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–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

18 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Ultra-large targeted DNA integrations in primary human cells.bioRxiv : the preprint server for biology · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Precision T cell correction platform for inborn errors of immunity.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  11. Article
  12. Article
  13. Review
  14. [Advancements in CRISPR-Cas9 for Fanconi anemia].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2025
    Review
  15. Article
  16. A Manual for Genome and Transcriptome Engineering.IEEE reviews in biomedical engineering · 2025
    Review
  17. Article
  18. Article
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

7 authors.

Mehmet E KarasuDepartment of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland.
Eléonore ToufektchanMolecular Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Yanyang ChenMolecular Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Alessandra AlbertelliDepartment of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland.
Grégoire CullotDepartment of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland.ORCID http://orcid.org/0000-0003-3925-705X
John MaciejowskiMolecular Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Jacob E CornDepartment of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland. jacob.corn@biol.ethz.ch.ORCID http://orcid.org/0000-0002-7798-5309

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Immune control and genomic instability at micronucleiR37CA261183 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI JOHN MACIEJOWSKI · 2022 to 2026
$2.4M
NCI NIH HHS P30 CA008748NCI NIH HHS R37 CA261183
6 · The paper itself

Abstract

CRISPR-Cas9-mediated homology-directed repair (HDR) can introduce desired mutations at targeted genomic sites, but achieving high efficiencies is a major hurdle in many cell types, including cells deficient in DNA repair activity. In this study, we used genome-wide screening in Fanconi anemia patient lymphoblastic cell lines to uncover suppressors of CRISPR-Cas9-mediated HDR. We found that a single exonuclease, TREX1, reduces HDR efficiency when the repair template is a single-stranded or linearized double-stranded DNA. TREX1 expression serves as a biomarker for CRISPR-Cas9-mediated HDR in that the high TREX1 expression present in many different cell types (such as U2OS, Jurkat, MDA-MB-231 and primary T cells as well as hematopoietic stem and progenitor cells) predicts poor HDR. Here we demonstrate rescue of HDR efficiency (ranging from two-fold to eight-fold improvement) either by TREX1 knockout or by the use of single-stranded DNA templates chemically protected from TREX1 activity. Our data explain why some cell types are easier to edit than others and indicate routes for increasing CRISPR-Cas9-mediated HDR in TREX1-expressing contexts.

Indexed as

CRISPR-Cas SystemsExodeoxyribonucleasesHomologous RecombinationPhosphoproteinsGene EditingHumansExodeoxyribonucleasesPhosphoproteinsthree prime repair exonuclease 1

Identifiers

PMID39134754
PMCPMC12263433

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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.