Evidence map›Paper›PMID 40858609›Full record

ArticleNature communications2025

Programmable epigenome editing by transient delivery of CRISPR epigenome editor ribonucleoproteins.

Da Xu, Swen Besselink, Gokul N Ramadoss, Philip H Dierks, Justin P Lubin, Rithu K Pattali, Jinna I Brim, Anna E Christenson, Peter J Colias, Izaiah J Ornelas and 4 more

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing 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

32 citing papers in PubMed.

  1. Review
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  15. Review
  16. Clinical translation of epigenome editing technologies.Current opinion in biomedical engineering · 2026
    Article
  17. Article
  18. Chemical reviews · 2026
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Da Xu *Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Swen Besselink *Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0009-0002-7815-0132
Gokul N RamadossGladstone Institutes, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-7506-2711
Philip H DierksGladstone Institutes, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-5903-8343
Justin P LubinDepartment of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0003-2311-1873
Rithu K PattaliDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Jinna I BrimDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0009-0005-4864-4192
Anna E ChristensonDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0002-1157-3168
Peter J ColiasDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Izaiah J OrnelasDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Carolyn D NguyenDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Sarah E ChasinsDepartment of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA, USA.ORCID http://orcid.org/0000-0003-0557-3580
Bruce R ConklinGladstone Institutes, San Francisco, CA, USA.
James K NuñezDepartment of Molecular and Cell Biology, University of California, Berkeley, CA, USA. jamesnunez@berkeley.edu.ORCID http://orcid.org/0000-0002-7396-6119

Funding

Project 3: Control of cardiac transcription by MEF2 and myocardinP01HL146366 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI SRIVASTAVA, DEEPAK · 2019 to 2023
$13.7M
Genetic Dissection of Cells and Organisms Training ProgramT32GM132022 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI Nicole King, NOAH K WHITEMAN · 2019 to 2026
$5.2M
Identifying Therapeutic Targets for RNA Splicing-Related CardiomyopathyR01HL130533 · NHLBI · J. DAVID GLADSTONE INSTITUTES · PI CONKLIN, BRUCE R · 2016 to 2019
$1.8M
C9orf72 frontotemporal dementia (FTD) and amyotrophic lateral sclerosis(ALS): using patient cells and CRISPR to reveal therapeutic approachesR01AG072052 · NIA · J. DAVID GLADSTONE INSTITUTES · PI CONKLIN, BRUCE R · 2024 to 2025
$1.4M
Mechanisms of epigenetic memory in human cellsR35GM155044 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI James Karlo Nunez · 2024 to 2026
$1.2M
Gladstone Institutes (J. David Gladstone Institutes) UCB 20240097NHLBI NIH HHS P01 HL146366NHLBI NIH HHS R01 HL130533NIA NIH HHS R01 AG072052NIGMS NIH HHS R35 GM155044NIGMS NIH HHS T32 GM132022U.S. Department of Health & Human Services | National Institutes of Health (NIH) R35GM155044-01
6 · The paper itself

Abstract

Programmable epigenome editors modify gene expression in mammalian cells by altering the local chromatin environment at target loci without inducing DNA breaks. However, the large size of CRISPR-based epigenome editors poses a challenge to their broad use in biomedical research and as future therapies. Here, we present Robust ENveloped Delivery of Epigenome-editor Ribonucleoproteins (RENDER) for transiently delivering programmable epigenetic repressors (CRISPRi, DNMT3A-3L-dCas9, CRISPRoff) and activator (TET1-dCas9) as ribonucleoprotein complexes into human cells to modulate gene expression. After rational engineering, we show that RENDER induces durable epigenetic silencing of endogenous genes across various human cell types, including primary T cells. Additionally, we apply RENDER to epigenetically repress endogenous genes in human stem cell-derived neurons, including the reduction of the neurodegenerative disease associated V337M-mutated Tau protein. Together, our RENDER platform advances the delivery of CRISPR-based epigenome editors into human cells, broadening the use of epigenome editing in fundamental research and therapeutic applications.

Indexed as

CRISPR-Cas SystemsEpigenesis, GeneticEpigenomeGene EditingRibonucleoproteinsDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3AEpigenome EditingHEK293 CellsHumansMixed Function OxygenasesNeuronsProto-Oncogene Proteinstau ProteinsDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNMT3A protein, humanMixed Function OxygenasesProto-Oncogene ProteinsRibonucleoproteinstau ProteinsTET1 protein, human

Identifiers

PMID40858609
PMCPMC12381050

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Registered trials

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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.