Evidence map›Paper›PMID 31101808›Full record

ArticleNature communications2019

Development of hRad51-Cas9 nickase fusions that mediate HDR without double-stranded breaks.

Holly A Rees, Wei-Hsi Yeh, David R Liu

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.

0numbers the graph read from it
0cells of the map it votes in
62citing papers in PubMed
9.9field-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

62 citing papers in PubMed, 141 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. The use of transgenic animals for xenotransplantation: An update.Animal models and experimental medicine · 2025
    Review
  7. Article
  8. Article
  9. Review
  10. On RNA-programmable gene modulation as a versatile set of principles targeting muscular dystrophies.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Strategies for precise gene edits in mammalian cells.Molecular therapy. Nucleic acids · 2023
    Review
  18. Article
  19. Article
  20. Mechanisms regulating the CRISPR-Cas systems.Frontiers in microbiology · 2023
    Review

2 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

3 authors at 1 institution in 1 country.

Holly A ReesMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
Wei-Hsi YehMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA.
David R LiuMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA. drliu@fas.harvard.edu.ORCID http://orcid.org/0000-0002-9943-7557
Broad Institute · US

Funding

Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human DiseaseRM1HG009490 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Brittany S. Adamson, Martin Joseph Ankrah Aryee · 2017 to 2026
$22.7M
Integrating Chemistry and Evolution to Illuminate Biology and Enable Novel TherapeuticsR35GM118062 · NIGMS · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2025
$6.4M
Expanding the Scope of Base EditingU01AI142756 · NIAID · BROAD INSTITUTE, INC. · PI LIU, DAVID R · 2018 to 2022
$2.1M
Continuous Evolution of Proteins with Novel Therapeutic PotentialR01EB022376 · NIBIB · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2019
$1.8M
NHGRI NIH HHS RM1 HG009490NIAID NIH HHS U01 AI142756NIBIB NIH HHS R01 EB022376NIGMS NIH HHS R35 GM118062
6 · The paper itself

Abstract

In mammalian cells, double-stranded DNA breaks (DSBs) are preferentially repaired through end-joining processes that generally lead to mixtures of insertions and deletions (indels) or other rearrangements at the cleavage site. In the presence of homologous DNA, homology-directed repair (HDR) can generate specific mutations, albeit typically with modest efficiency and a low ratio of HDR products:indels. Here, we develop hRad51 mutants fused to Cas9(D10A) nickase (RDN) that mediate HDR while minimizing indels. We use RDN to install disease-associated point mutations in HEK293T cells with comparable or better efficiency than Cas9 nuclease and a 2.7-to-53-fold higher ratio of desired HDR product:undesired byproducts. Across five different human cell types, RDN variants generally result in higher HDR:indel ratios and lower off-target activity than Cas9 nuclease, although HDR efficiencies remain strongly site- and cell type-dependent. RDN variants provide precision editing options in cell types amenable to HDR, especially when byproducts of DSBs must be minimized.

Indexed as

Recombinational DNA RepairCRISPR-Associated Protein 9DNA Breaks, Double-StrandedGene EditingGenetic EngineeringHEK293 CellsHeLa CellsHumansInduced Pluripotent Stem CellsK562 CellsRad51 RecombinaseRecombinant Fusion ProteinsTransfectionCRISPR-Associated Protein 9RAD51 protein, humanRad51 RecombinaseRecombinant Fusion Proteins

Identifiers

PMID31101808
PMCPMC6525190
OpenAlexW2945532708

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.