Evidence map›Paper›PMID 31767844›Full record

ArticleNature communications2019

Targeting specificity of APOBEC-based cytosine base editor in human iPSCs determined by whole genome sequencing.

Erica McGrath, Hyunsu Shin, Linyi Zhang, Je-Nie Phue, Wells W Wu, Rong-Fong Shen, Yoon-Young Jang, Javier Revollo, Zhaohui Ye

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 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.9field-weighted citation impact, top 8% 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

38 citing papers in PubMed, 65 citations in OpenAlex.

  1. Review
  2. A compact base editor rescues AATD-associated liver and lung disease in mouse models.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  3. Article
  4. Article
  5. Article
  6. CRISPR technologies for genome, epigenome and transcriptome editing.Nature reviews. Molecular cell biology · 2024
    Review
  7. Article
  8. CRISPR/Cas9 Landscape: Current State and Future Perspectives.International journal of molecular sciences · 2023
    Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Challenges of Gene Editing Therapies for Genodermatoses.International journal of molecular sciences · 2023
    Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Review
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 at 3 institutions in 1 country.

Erica McGrathDivision of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Hyunsu ShinDivision of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Linyi ZhangDivision of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Je-Nie PhueFacility for Biotechnology Resources, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.ORCID http://orcid.org/0000-0002-3502-3726
Wells W WuFacility for Biotechnology Resources, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Rong-Fong ShenFacility for Biotechnology Resources, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Yoon-Young JangDepartment of Oncology, Johns Hopkins School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-5462-2399
Javier RevolloDivision of Genetic and Molecular Toxicology, National Center for Toxicology Research, Food and Drug Administration, Jefferson, AR, USA. Javier.Revollo@fda.hhs.gov.
Zhaohui YeDivision of Cellular and Gene Therapies, Office of Tissues and Advanced Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA. Zhaohui.Ye@fda.hhs.gov.ORCID http://orcid.org/0000-0001-5272-9168
Center for Biologics Evaluation and Research · USJohns Hopkins University · USNational Center for Toxicological Research · US

Funding

Real Time Elucidation of Drug-Drug Interactions via Dual Reporter Cell Technology and Microfabricated ArraysR01EB023812 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI TONER, MEHMET, YARMUSH, MARTIN L · 2016 to 2019
$1.8M
A human iPSC-based model of Biliary AtresiaR03HD091264 · NICHD · JOHNS HOPKINS UNIVERSITY · PI JANG, YOON YOUNG · 2018 to 2019
$164k
NIBIB NIH HHS R01 EB023812NICHD NIH HHS R03 HD091264
6 · The paper itself

Abstract

DNA base editors have enabled genome editing without generating DNA double strand breaks. The applications of this technology have been reported in a variety of animal and plant systems, however, their editing specificity in human stem cells has not been studied by unbiased genome-wide analysis. Here we investigate the fidelity of cytidine deaminase-mediated base editing in human induced pluripotent stem cells (iPSCs) by whole genome sequencing after sustained or transient base editor expression. While base-edited iPSC clones without significant off-target modifications are identified, this study also reveals the potential of APOBEC-based base editors in inducing unintended point mutations outside of likely in silico-predicted CRISPR-Cas9 off-targets. The majority of the off-target mutations are C:G->T:A transitions or C:G->G:C transversions enriched for the APOBEC mutagenesis signature. These results demonstrate that cytosine base editor-mediated editing may result in unintended genetic modifications with distinct patterns from that of the conventional CRISPR-Cas nucleases.

Indexed as

AnimalsAPOBEC DeaminasesCRISPR-Cas SystemsCytidine DeaminaseCytosineDNA Breaks, Double-StrandedGene EditingGenome, HumanHumansInduced Pluripotent Stem CellsMutationPlant CellsReproducibility of ResultsWhole Genome SequencingAPOBEC DeaminasesCytidine DeaminaseCytosine

Identifiers

PMID31767844
PMCPMC6877639
OpenAlexW2991476931

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.