Evidence map›Paper›PMID 27662090›Full record

ArticleCell2016

Inheritable Silencing of Endogenous Genes by Hit-and-Run Targeted Epigenetic Editing.

Angelo Amabile, Alessandro Migliara, Paola Capasso, Mauro Biffi, Davide Cittaro, Luigi Naldini, Angelo Lombardo

Abstract read
In one paragraph

Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 307 papers.

0numbers the graph read from it
0cells of the map it votes in
307citing 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

307 citing papers in PubMed.

  1. Review
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  15. Clinical translation of epigenome editing technologies.Current opinion in biomedical engineering · 2026
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Epigenetic editing: from concept to clinic.Nature reviews. Drug discovery · 2026
    Review

247 more citing papers are in PubMed but not listed here.

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

7 authors.

Angelo AmabileSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy; Vita-Salute San Raffaele University, Via Olgettina 58, 20132 Milan, Italy.
Alessandro MigliaraSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy; Vita-Salute San Raffaele University, Via Olgettina 58, 20132 Milan, Italy.
Paola CapassoSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy.
Mauro BiffiSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy.
Davide CittaroCenter for Translational Genomics and Bioinformatics, IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy.
Luigi NaldiniSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy; Vita-Salute San Raffaele University, Via Olgettina 58, 20132 Milan, Italy. Electronic address: naldini.luigi@hsr.it.
Angelo LombardoSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy; Vita-Salute San Raffaele University, Via Olgettina 58, 20132 Milan, Italy. Electronic address: lombardo.angelo@hsr.it.

Funding

European Research Council 249845Telethon TGT16F01
6 · The paper itself

Abstract

Gene silencing is instrumental to interrogate gene function and holds promise for therapeutic applications. Here, we repurpose the endogenous retroviruses' silencing machinery of embryonic stem cells to stably silence three highly expressed genes in somatic cells by epigenetics. This was achieved by transiently expressing combinations of engineered transcriptional repressors that bind to and synergize at the target locus to instruct repressive histone marks and de novo DNA methylation, thus ensuring long-term memory of the repressive epigenetic state. Silencing was highly specific, as shown by genome-wide analyses, sharply confined to the targeted locus without spreading to nearby genes, resistant to activation induced by cytokine stimulation, and relieved only by targeted DNA demethylation. We demonstrate the portability of this technology by multiplex gene silencing, adopting different DNA binding platforms and interrogating thousands of genomic loci in different cell types, including primary T lymphocytes. Targeted epigenome editing might have broad application in research and medicine.

Indexed as

Gene SilencingCatalytic DomainDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3AEmbryonic Stem CellsGene EditingGene TargetingGenetic EngineeringHumansKruppel-Like Transcription FactorsRepressor ProteinsT-LymphocytesDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNMT3A protein, humanKruppel-Like Transcription FactorsRepressor ProteinsZNF10 protein, humanB2M-null cellsCRISPR/Cas9DNA methylationDNMT3Lepigenetic editinggene therapyKRAB-ZFP/KAP1permanent gene silencingTALETET1

Identifiers

PMID27662090
PMCPMC5039111

What OpenQuestion holds

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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.