Evidence map›Paper›PMID 29160308›Full record

ArticleNature2017

Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage.

Nicole M Gaudelli, Alexis C Komor, Holly A Rees, Michael S Packer, Ahmed H Badran, David I Bryson, David R Liu

Erratum issuedOpen access · greenAbstract readComparative Study
In one paragraph

Article in Nature, 2017. 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 2,403 papers.

0numbers the graph read from it
0cells of the map it votes in
2,403citing papers in PubMed
127.4field-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

2,403 citing papers in PubMed, 4,067 citations in OpenAlex.

  1. Review
  2. Article
  3. Electroporation for High-Efficiency Delivery of CRISPR to Hematopoietic Cells.Methods in molecular biology (Clifton, N.J.) · 2027
    Article
  4. Article
  5. Base Editing: Mechanisms and Therapeutic Applications.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
  6. Role of Chromatin-Associated RNAs in Eye Physiology and Pathology.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
  7. CRISPR/Cas Systems: Biological Basis and Genome Editing Applications.Methods in molecular biology (Clifton, N.J.) · 2027
    Review
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  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
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  15. Review
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2,343 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Nicole M GaudelliDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Alexis C KomorDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Holly A ReesDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Michael S PackerDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Ahmed H BadranDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
David I BrysonDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
David R LiuDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Howard Hughes Medical Institute · USBroad Institute · 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
MOLECULAR BIOPHYSICS TRAINING GRANTT32GM008313 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI MURTHY, VENKATESH N · 1989 to 2023
$14.6M
Integrating Chemistry and Evolution to Illuminate Biology and Enable Novel TherapeuticsR35GM118062 · NIGMS · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2025
$6.4M
Continuous Evolution of Proteins with Novel Therapeutic PotentialR01EB022376 · NIBIB · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2019
$1.8M
Development and validation of a precision genome editing platformF32GM112366 · NIGMS · HARVARD UNIVERSITY · PI KOMOR, ALEXIS C. · 2015 to 2017
$122k
Directed Evolution of Improved Orthogonal Aminoacyl-tRNASynthetases Through Phage Assisted Continuous Evolution (PACE)F32GM106621 · NIGMS · HARVARD UNIVERSITY · PI BRYSON, DAVID · 2015 to 2015
$54k
Howard Hughes Medical InstituteNHGRI NIH HHS RM1 HG009490NIBIB NIH HHS R01 EB022376NIGMS NIH HHS F32 GM106621NIGMS NIH HHS F32 GM112366NIGMS NIH HHS R35 GM118062NIGMS NIH HHS T32 GM008313
6 · The paper itself

Abstract

The spontaneous deamination of cytosine is a major source of transitions from C•G to T•A base pairs, which account for half of known pathogenic point mutations in humans. The ability to efficiently convert targeted A•T base pairs to G•C could therefore advance the study and treatment of genetic diseases. The deamination of adenine yields inosine, which is treated as guanine by polymerases, but no enzymes are known to deaminate adenine in DNA. Here we describe adenine base editors (ABEs) that mediate the conversion of A•T to G•C in genomic DNA. We evolved a transfer RNA adenosine deaminase to operate on DNA when fused to a catalytically impaired CRISPR-Cas9 mutant. Extensive directed evolution and protein engineering resulted in seventh-generation ABEs that convert targeted A•T base pairs efficiently to G•C (approximately 50% efficiency in human cells) with high product purity (typically at least 99.9%) and low rates of indels (typically no more than 0.1%). ABEs introduce point mutations more efficiently and cleanly, and with less off-target genome modification, than a current Cas9 nuclease-based method, and can install disease-correcting or disease-suppressing mutations in human cells. Together with previous base editors, ABEs enable the direct, programmable introduction of all four transition mutations without double-stranded DNA cleavage.

Indexed as

Adenosine DeaminaseBase PairingCell Line, TumorCRISPR-Associated ProteinsDNADNA CleavageGene EditingGenome, HumanHEK293 CellsHumansModels, MolecularPolymorphism, Single NucleotideAdenosine DeaminaseCRISPR-Associated ProteinsDNA

Identifiers

PMID29160308
PMCPMC5726555
OpenAlexW2766599608

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.