Evidence map›Paper›PMID 37537500›Full record

ArticleNature biotechnology2024

High-efficiency transgene integration by homology-directed repair in human primary cells using DNA-PKcs inhibition.

Sridhar Selvaraj, William N Feist, Sebastien Viel, Sriram Vaidyanathan, Amanda M Dudek, Marc Gastou, Sarah J Rockwood, Freja K Ekman, Aluya R Oseghale, Liwen Xu and 6 more

Open access · greenAbstract read
PubMed Publisher
In one paragraph

Article in Nature biotechnology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed, 1 pooled it
14.3field-weighted citation impact, top 1% 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

63 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.

  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. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. CRISPR and the Future of Cardiac Disease Therapy: A New Genetic Frontier.International journal of molecular sciences · 2026
    Review
  11. Review
  12. Article
  13. Article
  14. Ultra-large targeted DNA integrations in primary human cells.bioRxiv : the preprint server for biology · 2026
    Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Review

3 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

16 authors at 4 institutions in 3 countries.

Sridhar SelvarajDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
William N FeistDepartment of Pediatrics, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-5870-4460
Sebastien VielDepartment of Pediatrics, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-5085-443X
Sriram VaidyanathanDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
Amanda M DudekDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
Marc GastouDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
Sarah J RockwoodDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
Freja K EkmanDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
Aluya R OseghaleDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
Liwen XuDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
Mara Pavel-DinuDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
Sofia E LunaDepartment of Pediatrics, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-9173-9518
M Kyle CromerDepartment of Pediatrics, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-8198-5010
Ruhi SayanaDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
Natalia Gomez-OspinaDepartment of Pediatrics, Stanford University, Stanford, CA, USA.
Matthew H PorteusDepartment of Pediatrics, Stanford University, Stanford, CA, USA. mporteus@stanford.edu.ORCID http://orcid.org/0000-0002-3850-4648
California Institute for Regenerative Medicine · USNationwide Children's Hospital · USUniversité Claude Bernard Lyon 1 · FRUniversity of California, San Francisco · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Therapeutic applications of nuclease-based genome editing would benefit from improved methods for transgene integration via homology-directed repair (HDR). To improve HDR efficiency, we screened six small-molecule inhibitors of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a key protein in the alternative repair pathway of non-homologous end joining (NHEJ), which generates genomic insertions/deletions (INDELs). From this screen, we identified AZD7648 as the most potent compound. The use of AZD7648 significantly increased HDR (up to 50-fold) and concomitantly decreased INDELs across different genomic loci in various therapeutically relevant primary human cell types. In all cases, the ratio of HDR to INDELs markedly increased, and, in certain situations, INDEL-free high-frequency (>50%) targeted integration was achieved. This approach has the potential to improve the therapeutic efficacy of cell-based therapies and broaden the use of targeted integration as a research tool.

Indexed as

DNA-Activated Protein KinaseTransgenesDNA End-Joining RepairGene EditingHumansProtein Kinase InhibitorsRecombinational DNA RepairDNA-Activated Protein KinasePRKDC protein, humanProtein Kinase Inhibitors

Identifiers

PMID37537500
OpenAlexW4385555963

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.