Evidence map›Paper›PMID 31332326›Full record

ArticleNature biotechnology2019

Continuous evolution of base editors with expanded target compatibility and improved activity.

B W Thuronyi, Luke W Koblan, Jonathan M Levy, Wei-Hsi Yeh, Christine Zheng, Gregory A Newby, Christopher Wilson, Mantu Bhaumik, Olga Shubina-Oleinik, Jeffrey R Holt and 1 more

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Nature biotechnology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 217 papers.

0numbers the graph read from it
0cells of the map it votes in
217citing papers in PubMed
14.0field-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

217 citing papers in PubMed, 334 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Engineered Transformer Base Editor with Enhanced Editing Efficiency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Review
  18. Review
  19. Review
  20. Review

157 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

B W ThuronyiMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0003-0821-3791
Luke W Koblan *Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Jonathan M Levy *Merkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0002-8061-7953
Wei-Hsi YehMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Christine ZhengDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Gregory A NewbyMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0001-7869-2615
Christopher WilsonMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0002-8012-2440
Mantu BhaumikDepartment of Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Olga Shubina-OleinikDepartments of Otolaryngology and Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
Jeffrey R HoltDepartments of Otolaryngology and Neurology, F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-7182-8011
David R LiuMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of Harvard and MIT, Cambridge, MA, USA. drliu@fas.harvard.edu.ORCID 0000-0002-9943-7557
Broad Institute · USBoston Children's Hospital · USHarvard University · 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
TMC gene function in sensory hair cellsR01DC013521 · NIDCD · BOSTON CHILDREN'S HOSPITAL · PI JEFFREY R HOLT · 2013 to 2026
$6.0M
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
Continuous Evolution of Proteins with Novel Therapeutic PotentialR01EB022376 · NIBIB · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2019
$1.8M
Howard Hughes Medical InstituteNHGRI NIH HHS RM1 HG009490NIAID NIH HHS U01 AI142756NIBIB NIH HHS R01 EB022376NIDCD NIH HHS R01 DC013521NIGMS NIH HHS R35 GM118062NIGMS NIH HHS T32 GM095450
6 · The paper itself

Abstract

Base editors use DNA-modifying enzymes targeted with a catalytically impaired CRISPR protein to precisely install point mutations. Here, we develop phage-assisted continuous evolution of base editors (BE-PACE) to improve their editing efficiency and target sequence compatibility. We used BE-PACE to evolve cytosine base editors (CBEs) that overcome target sequence context constraints of canonical CBEs. One evolved CBE, evoAPOBEC1-BE4max, is up to 26-fold more efficient at editing cytosine in the GC context, a disfavored context for wild-type APOBEC1 deaminase, while maintaining efficient editing in all other sequence contexts tested. Another evolved deaminase, evoFERNY, is 29% smaller than APOBEC1 and edits efficiently in all tested sequence contexts. We also evolved a CBE based on CDA1 deaminase with much higher editing efficiency at difficult target sites. Finally, we used data from evolved CBEs to illuminate the relationship between deaminase activity, base editing efficiency, editing window width and byproduct formation. These findings establish a system for rapid evolution of base editors and inform their use and improvement.

Indexed as

Directed Molecular EvolutionGene EditingAdenosine DeaminaseAnimalsBase SequenceCell LineCRISPR-Cas SystemsGene Expression Regulation, EnzymologicGene TargetingHumansINDEL MutationMiceAdenosine Deaminase

Identifiers

PMID31332326
PMCPMC6728210
OpenAlexW2963629338

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.