Evidence map›Paper›PMID 39883775›Full record

ArticleScience (New York, N.Y.)2025

Randomizing the human genome by engineering recombination between repeat elements.

Jonas Koeppel, Raphael Ferreira, Thomas Vanderstichele, Lisa Maria Riedmayr, Elin Madli Peets, Gareth Girling, Juliane Weller, Pierre Murat, Fabio Giuseppe Liberante, Tom Ellis and 2 more

Abstract read
PubMed Publisher
In one paragraph

Article in Science (New York, N.Y.), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing 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

21 citing papers in PubMed.

  1. Article
  2. Genomic repeats for single-cell molecular recording.bioRxiv : the preprint server for biology · 2026
    Article
  3. Synthetic Regulatory Genomics.Annual review of genomics and human genetics · 2026
    Review
  4. Review
  5. Article
  6. Article
  7. Gigabase-scale deletion scanning of the human genome.bioRxiv : the preprint server for biology · 2026
    Article
  8. Review
  9. Gene-sized editing for the therapy of genetic diseases.Functional & integrative genomics · 2026
    Review
  10. Review
  11. Epigenome editing based treatment: Progresses and challenges.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Review
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Jonas Koeppel *Wellcome Sanger Institute, Hinxton, UK.ORCID 0000-0003-1306-3994
Raphael Ferreira *Harvard Medical School, Department of Genetics, Boston, MA, USA.ORCID 0000-0001-9881-6232
Thomas VandersticheleWellcome Sanger Institute, Hinxton, UK.ORCID 0009-0007-8235-2745
Lisa Maria RiedmayrHarvard Medical School, Department of Genetics, Boston, MA, USA.
Elin Madli PeetsWellcome Sanger Institute, Hinxton, UK.ORCID 0000-0002-3479-1969
Gareth GirlingWellcome Sanger Institute, Hinxton, UK.ORCID 0000-0002-8031-1903
Juliane WellerWellcome Sanger Institute, Hinxton, UK.ORCID 0000-0002-1310-6168
Pierre MuratWellcome Sanger Institute, Hinxton, UK.
Fabio Giuseppe LiberanteWellcome Sanger Institute, Hinxton, UK.ORCID 0000-0002-0192-5385
Tom EllisWellcome Sanger Institute, Hinxton, UK.ORCID 0000-0001-5392-976X
George McDonald ChurchHarvard Medical School, Department of Genetics, Boston, MA, USA.ORCID 0000-0001-6232-9969
Leopold PartsWellcome Sanger Institute, Hinxton, UK.ORCID 0000-0002-2618-670X

Funding

Wellcome Trust 220540/Z/20/A
6 · The paper itself

Abstract

We lack tools to edit DNA sequences at scales necessary to study 99% of the human genome that is noncoding. To address this gap, we applied CRISPR prime editing to insert recombination handles into repetitive sequences, up to 1697 per cell line, which enables generating large-scale deletions, inversions, translocations, and circular DNA. Recombinase induction produced more than 100 stochastic megabase-sized rearrangements in each cell. We tracked these rearrangements over time to measure selection pressures, finding a preference for shorter variants that avoided essential genes. We characterized 29 clones with multiple rearrangements, finding an impact of deletions on expression of genes in the variant but not on nearby genes. This genome-scrambling strategy enables large deletions, sequence relocations, and the insertion of regulatory elements to explore genome dispensability and organization.

Indexed as

Gene EditingGenome, HumanRecombination, GeneticRepetitive Sequences, Nucleic AcidCell LineCRISPR-Cas SystemsHumansSequence DeletionTranslocation, Genetic

Identifiers

What OpenQuestion holds

Textmetadata
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.