Evidence map›Paper›PMID 32042165›Full record

ArticleNature biotechnology2020

Evaluation and minimization of Cas9-independent off-target DNA editing by cytosine base editors.

Jordan L Doman, Aditya Raguram, Gregory A Newby, David R Liu

Open access · greenAbstract read
In one paragraph

Article in Nature biotechnology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 317 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
317citing papers in PubMed, 1 pooled it
22.9field-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

317 citing papers in PubMed, 1 synthesis or guideline pooled it, 439 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. Base Editing: Mechanisms and Therapeutic Applications.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. bioRxiv : the preprint server for biology · 2026
    Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Compact 9dBEs Enable Efficient and Precise Genome Editing in Mammalian Cells and In Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

257 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

4 authors at 1 institution in 1 country.

Jordan L Doman *Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-9887-0391
Aditya Raguram *Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Gregory A NewbyMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-7869-2615
David R LiuMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA. drliu@fas.harvard.edu.ORCID http://orcid.org/0000-0002-9943-7557
Broad Institute · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
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
Principles of Scientific Citizenship: Ethics, Communication, and Leadership for ScientistsT32GM095450 · NIGMS · HARVARD UNIVERSITY · PI WALKER, SUZANNE · 2011 to 2020
$3.5M
Expanding the Scope of Base EditingU01AI142756 · NIAID · BROAD INSTITUTE, INC. · PI LIU, DAVID R · 2018 to 2022
$2.1M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA014051NHGRI NIH HHS RM1 HG009490NIAID NIH HHS U01 AI142756NIGMS NIH HHS R35 GM118062NIGMS NIH HHS T32 GM095450
6 · The paper itself

Abstract

Cytosine base editors (CBEs) enable targeted C•G-to-T•A conversions in genomic DNA. Recent studies report that BE3, the original CBE, induces a low frequency of genome-wide Cas9-independent off-target C•G-to-T•A mutation in mouse embryos and in rice. Here we develop multiple rapid, cost-effective methods to screen the propensity of different CBEs to induce Cas9-independent deamination in Escherichia coli and in human cells. We use these assays to identify CBEs with reduced Cas9-independent deamination and validate via whole-genome sequencing that YE1, a narrowed-window CBE variant, displays background levels of Cas9-independent off-target editing. We engineered YE1 variants that retain the substrate-targeting scope of high-activity CBEs while maintaining minimal Cas9-independent off-target editing. The suite of CBEs characterized and engineered in this study collectively offer ~10-100-fold lower average Cas9-independent off-target DNA editing while maintaining robust on-target editing at most positions targetable by canonical CBEs, and thus are especially promising for applications in which off-target editing must be minimized.

Indexed as

CRISPR-Associated Protein 9CytosineEscherichia coliGene EditingHEK293 CellsHumansMutationWhole Genome SequencingCRISPR-Associated Protein 9Cytosine

Identifiers

PMID32042165
PMCPMC7335424
OpenAlexW3004494456

What OpenQuestion holds

Textmetadata
LicenceTDM
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.