Evidence map›Paper›PMID 38402281›Full record

ArticleNature communications2024

Phage-assisted evolution of highly active cytosine base editors with enhanced selectivity and minimal sequence context preference.

Emily Zhang, Monica E Neugebauer, Nicholas A Krasnow, David R Liu

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
11.5field-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

48 citing papers in PubMed, 49 citations in OpenAlex.

  1. Review
  2. bioRxiv : the preprint server for biology · 2026
    Article
  3. Engineered Transformer Base Editor with Enhanced Editing Efficiency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Cytosine base editing of LPA in transgenic mice averts large deletions.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  12. Anti-CRISPR-mediated continuous directed evolution of CRISPR-Cas9 in human cells.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
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.

Emily ZhangMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-9053-1336
Monica E NeugebauerMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nicholas A KrasnowMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
David R LiuMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA. drliu@fas.harvard.edu.ORCID 0000-0002-9943-7557
Broad Institute · US

Funding

Therapeutic editing to lower PrP in prion disease: Administrative CoreU19NS132315 · NINDS · BROAD INSTITUTE, INC. · PI Sonia Minikel Vallabh · 2023 to 2026
$39.1M
Viral Vector and Regulatory CoreU19NS132304 · NINDS · JACKSON LABORATORY · PI Cathleen M Lutz · 2023 to 2026
$24.0M
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
ePACE: automation platforms for adaptable and scalable continuous evolution of biomolecules with therapeutic potentialR01EB027793 · NIBIB · BROAD INSTITUTE, INC. · PI Ahmad Samir Khalil, DAVID R LIU · 2019 to 2026
$6.1M
PedGeneRx - Admin Supplement to Base Editing and Prime Editing for Sickle Cell Disease R01R01HL156647 · NHLBI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI Agnieszka Czechowicz, DAVID R LIU · 2021 to 2026
$4.8M
Continuous Evolution of Proteins with Novel Therapeutic PotentialR01EB031172 · NIBIB · BROAD INSTITUTE, INC. · PI LIU, DAVID R · 2021 to 2024
$2.5M
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
Directed Evolution of an Epitranscriptomic ToolkitF32GM143776 · NIGMS · BROAD INSTITUTE, INC. · PI NEUGEBAUER, MONICA · 2021 to 2023
$205k
NHGRI NIH HHS RM1 HG009490NHLBI NIH HHS R01 HL156647NIAID NIH HHS U01 AI142756NIBIB NIH HHS R01 EB022376NIBIB NIH HHS R01 EB027793NIBIB NIH HHS R01 EB031172NIGMS NIH HHS F32 GM143776NIGMS NIH HHS R35 GM118062NINDS NIH HHS U19 NS132304NINDS NIH HHS U19 NS132315
6 · The paper itself

Abstract

TadA-derived cytosine base editors (TadCBEs) enable programmable C•G-to-T•A editing while retaining the small size, high on-target activity, and low off-target activity of TadA deaminases. Existing TadCBEs, however, exhibit residual A•T-to-G•C editing at certain positions and lower editing efficiencies at some sequence contexts and with non-SpCas9 targeting domains. To address these limitations, we use phage-assisted evolution to evolve CBE6s from a TadA-mediated dual cytosine and adenine base editor, discovering mutations at N46 and Y73 in TadA that prevent A•T-to-G•C editing and improve C•G-to-T•A editing with expanded sequence-context compatibility, respectively. In E. coli, CBE6 variants offer high C•G-to-T•A editing and no detected A•T-to-G•C editing in any sequence context. In human cells, CBE6 variants exhibit broad Cas domain compatibility and retain low off-target editing despite exceeding BE4max and previous TadCBEs in on-target editing efficiency. Finally, we show that the high selectivity of CBE6 variants is well-suited for therapeutically relevant stop codon installation without creating unwanted missense mutations from residual A•T-to-G•C editing.

Indexed as

BacteriophagesGene EditingCRISPR-Cas SystemsCytosineEscherichia coliHumansCytosine

Identifiers

PMID38402281
PMCPMC10894238
OpenAlexW4392129257

What OpenQuestion holds

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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.