Evidence map›Paper›PMID 36418298›Full record

ArticleNature communications2022

Compact zinc finger base editors that edit mitochondrial or nuclear DNA in vitro and in vivo.

Julian C W Willis, Pedro Silva-Pinheiro, Lily Widdup, Michal Minczuk, David R Liu

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
5.5field-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

35 citing papers in PubMed, 65 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. High-efficiency base editing for nuclear and mitochondrial DNA with an optimized DYW-like deaminase.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  11. Therapies for Mitochondrial Disease: Past, Present, and Future.Journal of inherited metabolic disease · 2025
    Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Disease models of Leigh syndrome: From yeast to organoids.Journal of inherited metabolic disease · 2024
    Review
  19. Article
  20. Review
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

5 authors at 2 institutions in 2 countries.

Julian C W WillisMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-2655-2183
Pedro Silva-PinheiroMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.ORCID 0000-0002-0872-5749
Lily WiddupMerkin Institute of Transformative Technologies in Healthcare, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Michal MinczukMRC Mitochondrial Biology Unit, University of Cambridge, Cambridge, UK.ORCID 0000-0001-8242-1420
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 · USUniversity of Cambridge · GB

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
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
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
Medical Research Council MC_UU_00015/4Medical Research Council MC_UU_00015/7NHGRI NIH HHS RM1 HG009490NIAID NIH HHS U01 AI142756NIBIB NIH HHS R01 EB027793NIBIB NIH HHS R01 EB031172NIGMS NIH HHS R35 GM118062
6 · The paper itself

Abstract

DddA-derived cytosine base editors (DdCBEs) use programmable DNA-binding TALE repeat arrays, rather than CRISPR proteins, a split double-stranded DNA cytidine deaminase (DddA), and a uracil glycosylase inhibitor to mediate C•G-to-T•A editing in nuclear and organelle DNA. Here we report the development of zinc finger DdCBEs (ZF-DdCBEs) and the improvement of their editing performance through engineering their architectures, defining improved ZF scaffolds, and installing DddA activity-enhancing mutations. We engineer variants with improved DNA specificity by integrating four strategies to reduce off-target editing. We use optimized ZF-DdCBEs to install or correct disease-associated mutations in mitochondria and in the nucleus. Leveraging their small size, we use a single AAV9 to deliver into heart, liver, and skeletal muscle in post-natal mice ZF-DdCBEs that efficiently install disease-associated mutations. While off-target editing of ZF-DdCBEs is likely too high for therapeutic applications, these findings demonstrate a compact, all-protein base editing research tool for precise editing of organelle or nuclear DNA without double-strand DNA breaks.

Indexed as

CRISPR-Cas SystemsGene EditingAnimalsCytosineDNAMiceMitochondriaZinc FingersCytosineDNA

Identifiers

PMID36418298
PMCPMC9684478
OpenAlexW4309890738

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.