Evidence map›Paper›PMID 32315033›Full record

ArticleNucleic acids research2020

Enabling large-scale genome editing at repetitive elements by reducing DNA nicking.

Cory J Smith, Oscar Castanon, Khaled Said, Verena Volf, Parastoo Khoshakhlagh, Amanda Hornick, Raphael Ferreira, Chun-Ting Wu, Marc Güell, Shilpa Garg and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 6% 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

39 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.

  1. Pooled it
  2. Genomic repeats for single-cell molecular recording.bioRxiv : the preprint server for biology · 2026
    Article
  3. Review
  4. Article
  5. Article
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  7. Review
  8. Article
  9. Article
  10. The design and engineering of synthetic genomes.Nature reviews. Genetics · 2025
    Review
  11. Article
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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 4 institutions in 4 countries.

Cory J SmithDepartment of Genetics, Harvard Medical School, Boston, MA, 02115 USA.
Oscar CastanonDepartment of Genetics, Harvard Medical School, Boston, MA, 02115 USA.
Khaled SaidDepartment of Genetics, Harvard Medical School, Boston, MA, 02115 USA.
Verena VolfDepartment of Genetics, Harvard Medical School, Boston, MA, 02115 USA.
Parastoo KhoshakhlaghDepartment of Genetics, Harvard Medical School, Boston, MA, 02115 USA.
Amanda HornickDepartment of Genetics, Harvard Medical School, Boston, MA, 02115 USA.
Raphael FerreiraDepartment of Biology and Biological Engineering, Chalmers University of Technology, SE412 96 Gothenburg, Sweden.
Chun-Ting WuDepartment of Genetics, Harvard Medical School, Boston, MA, 02115 USA.
Marc GüellPompeu Fabra University, Barcelona Biomedical Research Park, 08003 Barcelona, Spain.
Shilpa GargDepartment of Genetics, Harvard Medical School, Boston, MA, 02115 USA.
Alex H M NgDepartment of Genetics, Harvard Medical School, Boston, MA, 02115 USA.
Hannu MyllykallioLOB, Ecole Polytechnique, CNRS, INSERM, Institut Polytechnique de Paris, 91128 Palaiseau, France.
George M ChurchDepartment of Genetics, Harvard Medical School, Boston, MA, 02115 USA.
Harvard University · USCentre National de la Recherche Scientifique · FRBarcelona Biomedical Research Park · ESChalmers University of Technology · SE

Funding

Center for Genomically Engineered OrgansRM1HG008525 · NHGRI · HARVARD MEDICAL SCHOOL · PI CHURCH, GEORGE M · 2015 to 2019
$10.2M
NHGRI NIH HHS RM1 HG008525
6 · The paper itself

Abstract

To extend the frontier of genome editing and enable editing of repetitive elements of mammalian genomes, we made use of a set of dead-Cas9 base editor (dBE) variants that allow editing at tens of thousands of loci per cell by overcoming the cell death associated with DNA double-strand breaks and single-strand breaks. We used a set of gRNAs targeting repetitive elements-ranging in target copy number from about 32 to 161 000 per cell. dBEs enabled survival after large-scale base editing, allowing targeted mutations at up to ∼13 200 and ∼12 200 loci in 293T and human induced pluripotent stem cells (hiPSCs), respectively, three orders of magnitude greater than previously recorded. These dBEs can overcome current on-target mutation and toxicity barriers that prevent cell survival after large-scale genome engineering.

Indexed as

RetroelementsCell SurvivalCRISPR-Associated ProteinsCRISPR-Cas SystemsEndodeoxyribonucleasesGene EditingHEK293 CellsHumansInduced Pluripotent Stem CellsMutationRNACRISPR-Associated ProteinsEndodeoxyribonucleasesRetroelementsRNA

Identifiers

PMID32315033
PMCPMC7229841
OpenAlexW3016711432

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.