Evidence map›Paper›PMID 37474806›Full record

ArticleNature methods2023

Efficient high-precision homology-directed repair-dependent genome editing by HDRobust.

Stephan Riesenberg, Philipp Kanis, Dominik Macak, Damian Wollny, Dorothee Düsterhöft, Johannes Kowalewski, Nelly Helmbrecht, Tomislav Maricic, Svante Pääbo

Abstract read
In one paragraph

Article in Nature methods, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 1 pooled it
–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

65 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. CRISPR for cystic fibrosis: Advances and insights from a systematic review.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Pooled it
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. A primer on prime: A prime editing update from advances to first-in-human trial.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Review
  12. Article
  13. Review
  14. Article
  15. Ultra-large targeted DNA integrations in primary human cells.bioRxiv : the preprint server for biology · 2026
    Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

5 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

9 authors.

Stephan RiesenbergDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany. stephan_riesenberg@eva.mpg.de.ORCID http://orcid.org/0000-0001-8171-1717
Philipp KanisDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.ORCID http://orcid.org/0000-0003-4705-4447
Dominik MacakDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.ORCID http://orcid.org/0009-0001-7266-8515
Damian WollnyDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
Dorothee DüsterhöftDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
Johannes KowalewskiDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
Nelly HelmbrechtDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.ORCID http://orcid.org/0000-0002-5384-8430
Tomislav MaricicDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.ORCID http://orcid.org/0000-0003-3267-0474
Svante PääboDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.ORCID http://orcid.org/0000-0002-4670-6311

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Homology-directed repair (HDR), a method for repair of DNA double-stranded breaks can be leveraged for the precise introduction of mutations supplied by synthetic DNA donors, but remains limited by low efficiency and off-target effects. In this study, we report HDRobust, a high-precision method that, via the combined transient inhibition of nonhomologous end joining and microhomology-mediated end joining, resulted in the induction of point mutations by HDR in up to 93% (median 60%, s.e.m. 3) of chromosomes in populations of cells. We found that, using this method, insertions, deletions and rearrangements at the target site, as well as unintended changes at other genomic sites, were largely abolished. We validated this approach for 58 different target sites and showed that it allows efficient correction of pathogenic mutations in cells derived from patients suffering from anemia, sickle cell disease and thrombophilia.

Indexed as

CRISPR-Cas SystemsGene EditingDNADNA Breaks, Double-StrandedDNA End-Joining RepairHumansRecombinational DNA RepairDNA

Identifiers

PMID37474806
PMCPMC10482697

What OpenQuestion holds

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Registered trials

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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.