# Epigenetic editing (durable gene silencing)

Source: https://onco.cc/technologies/epigenetic-editing/  
OnCo record `epigenetic-editing` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Switching a gene off for good without changing the DNA sequence, by writing chemical marks onto it.

## Summary

CRISPRoff-style effectors fuse a dead Cas protein to DNA methyltransferase and repressor domains, imposing heritable silencing that survives cell division. Tune Therapeutics and Chroma Medicine took the approach into the clinic in hepatitis B, not cancer. In oncology it is an attractive route to silence undruggable drivers such as MYC, but no oncology trial had been registered by September 2026, and silencing would have to reach essentially every tumour cell to matter.

## Fields

- Kind: Technology
- Status: concept
- Last checked: 2026-09-08
- Tags: frontier; radical
- Principle: dCas9 fused to DNMT3A/3L and KRAB deposits CpG methylation and repressive histone marks at a promoter; the silenced state is copied to daughter cells.
- Strengths: No DNA cut, so no translocation risk; Potentially reversible; Reaches transcription factors that have no drug pocket
- Limitations: No oncology trial yet (2026); Delivery to solid tumours unsolved; Escape by cells that lose the mark or the dependency

## Sources

- ClinicalTrials.gov: epigenetic editing: https://clinicaltrials.gov/search?term=epigenetic%20editing

## Connected records

- fronts: [Epigenetic & Transcriptional Therapy](https://onco.cc/fronts/epigenetics/), [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- technologies: [CRISPR functional genomics](https://onco.cc/technologies/crispr-screens/), [Epigenetic drugs (HDAC, DNMT, EZH2, IDH, menin, BET)](https://onco.cc/technologies/epigenetic-drugs/), [Programmable DNA-targeting therapeutics](https://onco.cc/technologies/programmable-dna-targeting-therapeutics/)
- roadmaps: [Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome](https://onco.cc/roadmaps/epigenetics-roadmap/), [Radical oncology: what could change the war by 2035](https://onco.cc/roadmaps/frontier-2035/)
- terms: [Epigenetic progenitor theory: cancer without a first mutation](https://onco.cc/terms/epigenetic-progenitor-theory/)

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