Evidence map›Paper›PMID 27804970›Full record

ArticleNature communications2016

Engineering and optimising deaminase fusions for genome editing.

Luhan Yang, Adrian W Briggs, Wei Leong Chew, Prashant Mali, Marc Guell, John Aach, Daniel Bryan Goodman, David Cox, Yinan Kan, Emal Lesha and 3 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2016. 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 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

50 citing papers in PubMed, 75 citations in OpenAlex.

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  19. Precise genome editing with base editors.Medical review (2021) · 2023
    Review
  20. Association ofAnnals of translational medicine · 2022
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 3 countries.

Luhan YangDepartment of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Adrian W BriggsDepartment of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Wei Leong ChewDepartment of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.ORCID 0000-0002-4774-7959
Prashant MaliDepartment of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Marc GuellDepartment of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
John AachDepartment of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Daniel Bryan GoodmanDepartment of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
David CoxHarvard-MIT Division of Health Science and Technology, Cambridge, Massachusetts 02139, USA.
Yinan KanDepartment of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Emal LeshaDepartment of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Venkataramanan SoundararajanDepartment of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Feng ZhangBroad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
George ChurchDepartment of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA.
Harvard University · USFidal · FRAgency for Science, Technology and Research · SGBroad Institute · USHarvard–MIT Division of Health Sciences and Technology · US

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Probing Neuropsychiatric Diseases Using Targeted Epigenome and Genome EngineeringDP1MH100706 · NIMH · BROAD INSTITUTE, INC. · PI ZHANG, FENG · 2012 to 2016
$4.3M
NIGMS NIH HHS T32 GM007753NIMH NIH HHS DP1 MH100706
6 · The paper itself

Abstract

Precise editing is essential for biomedical research and gene therapy. Yet, homology-directed genome modification is limited by the requirements for genomic lesions, homology donors and the endogenous DNA repair machinery. Here we engineered programmable cytidine deaminases and test if we could introduce site-specific cytidine to thymidine transitions in the absence of targeted genomic lesions. Our programmable deaminases effectively convert specific cytidines to thymidines with 13% efficiency in Escherichia coli and 2.5% in human cells. However, off-target deaminations were detected more than 150 bp away from the target site. Moreover, whole genome sequencing revealed that edited bacterial cells did not harbour chromosomal abnormalities but demonstrated elevated global cytidine deamination at deaminase intrinsic binding sites. Therefore programmable deaminases represent a promising genome editing tool in prokaryotes and eukaryotes. Future engineering is required to overcome the processivity and the intrinsic DNA binding affinity of deaminases for safer therapeutic applications.

Indexed as

Gene EditingGenetic EngineeringBase SequenceCytidine DeaminaseDeaminationEscherichia coliGenome, HumanHEK293 CellsHumansRecombinant Fusion ProteinsSubstrate SpecificityCytidine DeaminaseRecombinant Fusion Proteins

Identifiers

PMID27804970
PMCPMC5097136
OpenAlexW2548327551

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.