Evidence map›Paper›PMID 34663942›Full record

ArticleNature chemical biology2021

Controllable genome editing with split-engineered base editors.

Kiara N Berríos, Niklaus H Evitt, Rachel A DeWeerd, Diqiu Ren, Meiqi Luo, Aleksia Barka, Tong Wang, Caroline R Bartman, Yemin Lan, Abby M Green and 2 more

Abstract read
In one paragraph

Article in Nature chemical biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
–field-weighted citation impact
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

33 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Efforts to Downsize Base Editors for Clinical Applications.International journal of molecular sciences · 2025
    Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  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

12 authors.

Kiara N BerríosGraduate Group in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-0684-5413
Niklaus H EvittGraduate Group in Cell and Molecular Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-2117-9073
Rachel A DeWeerdDepartment of Pediatrics, Washington University School of Medicine, St. Louis, MI, USA.ORCID http://orcid.org/0000-0001-9309-113X
Diqiu RenDepartment of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Meiqi LuoDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Aleksia BarkaDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-3388-0062
Tong WangGraduate Group in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Caroline R BartmanEpigenetics Institute, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-2147-6003
Yemin LanEpigenetics Institute, Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Abby M GreenDepartment of Pediatrics, Washington University School of Medicine, St. Louis, MI, USA.
Junwei ShiDepartment of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. jushi@upenn.edu.ORCID http://orcid.org/0000-0002-8427-6316
Rahul M KohliDepartment of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. rkohli@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0002-7689-5678

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007170 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BRASS, LAWRENCE F · 1985 to 2022
$54.0M
Ultra low-input epigenetic sequencing with combined enzymatic and long-read technologiesR01HG010646 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI Gang Fang, Rahul Manu Kohli · 2019 to 2026
$3.9M
Engineering Efficient and Controllable Base EditorsR01GM138908 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI KOHLI, RAHUL MANU · 2021 to 2024
$1.9M
Molecular Interactions of APOBEC3 Enzymes with the Cancer GenomeK08CA212299 · NCI · WASHINGTON UNIVERSITY · PI GREEN, ABBY MARGARET · 2016 to 2020
$744k
Multiplexing CRISPR/Cas9-based Continuous Evolution for Improved Epigenome EditingF30HG011578 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI EVITT, NIKLAUS HOYT · 2020 to 2021
$95k
NCI NIH HHS K08 CA212299NHGRI NIH HHS F30 HG011578NHGRI NIH HHS R01 HG010646NIGMS NIH HHS R01 GM138908NIGMS NIH HHS T32 GM007170
6 · The paper itself

Abstract

DNA deaminase enzymes play key roles in immunity and have recently been harnessed for their biotechnological applications. In base editors (BEs), the combination of DNA deaminase mutator activity with CRISPR-Cas localization confers the powerful ability to directly convert one target DNA base into another. While efforts have been made to improve targeting efficiency and precision, all BEs so far use a constitutively active DNA deaminase. The absence of regulatory control over promiscuous deaminase activity remains a major limitation to accessing the widespread potential of BEs. Here, we reveal sites that permit splitting of DNA cytosine deaminases into two inactive fragments, whose reapproximation reconstitutes activity. These findings allow for the development of split-engineered BEs (seBEs), which newly enable small-molecule control over targeted mutator activity. We show that the seBE strategy facilitates robust regulated editing with BE scaffolds containing diverse deaminases, offering a generalizable solution for temporally controlling precision genome editing.

Indexed as

BiotechnologyCRISPR-Cas SystemsCytosineDNADNA Breaks, Double-StrandedEscherichia coliGene EditingNucleic Acid ConformationNucleoside DeaminasesSirolimusCytosineDNANucleoside DeaminasesSirolimus

Identifiers

PMID34663942
PMCPMC8981362

What OpenQuestion holds

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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.