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Updated: Jun 13, 2025

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers

Published on: September 20, 2018

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Targeted transcriptional downregulation of MYC using epigenomic controllers demonstrates antitumor activity in

William Senapedis1, Kayleigh M Gallagher2,3, Elmer Figueroa2,4

  • 1Omega Therapeutics, Cambridge, MA, USA. wsenapedis@omegatx.com.

Nature Communications
|September 16, 2024
PubMed

Insights

A novel epigenomic controller (EC) targets the MYC gene in hepatocellular carcinoma (HCC). This mRNA medicine effectively downregulates MYC, showing significant antitumor activity in preclinical models.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Medicine

Background:

  • The c-MYC (MYC) oncogene is frequently dysregulated in hepatocellular carcinoma (HCC) and other cancers.
  • MYC's role as a master regulator makes it a critical, yet challenging, therapeutic target.
  • MYC expression is epigenetically controlled within Insulated Genomic Domains (IGDs).

Purpose of the Study:

  • To develop a programmable epigenomic mRNA medicine (epigenomic controller, EC) to target and downregulate MYC in HCC.
  • To investigate the therapeutic potential of MYC-targeted EC as monotherapy and in combination treatments.

Main Methods:

  • Utilized an epigenomic controller (EC) mRNA medicine designed to modify MYC IGD sub-elements.
  • Induced methylation of MYC regulatory elements to achieve durable transcriptional downregulation.
  • Evaluated antitumor activity in preclinical models of HCC.

Main Results:

  • The MYC-targeted EC demonstrated significant antitumor activity in HCC models.
  • Effective durable downregulation of MYC mRNA transcription was achieved.
  • Combination therapy with tyrosine kinase or immune checkpoint inhibitors enhanced efficacy.

Conclusions:

  • Epigenomic controllers represent a promising therapeutic strategy for MYC-driven cancers like HCC.
  • This programmable mRNA medicine approach offers a new framework for cancer therapeutics.
  • Further clinical development of MYC-targeting ECs in HCC patients is warranted.

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