OMGA - Omega Therapeutics Showcases Bidirectional and Multiplexed Epigenomic Control of Gene Expression in Preclinical Models of Liver Inflammation and Fibrosis | Benzinga
First-ever demonstration of sustained pre-transcriptional upregulation of gene expression by an epigenomic controller in both in vitro and in vivo models of liver fibrosis
Single epigenomic controller demonstrated ability to simultaneously regulate the expression of chemokines CXCL9-11 across in vitro models of liver inflammation
CAMBRIDGE, Mass., Nov. 13, 2023 (GLOBE NEWSWIRE) -- Omega Therapeutics, Inc. (NASDAQ:OMGA) ("Omega"), a clinical-stage biotechnology company pioneering the development of a new class of programmable epigenomic mRNA medicines, today announced the presentation of new preclinical data from two different programs that demonstrated sustained upregulation of gene expression and coordinated pre-transcriptional downregulation of multiple genes in models of liver fibrosis and inflammation, respectively, at the American Association for the Study of Liver Diseases' (AASLD) The Liver Meeting® 2023, taking place in Boston, Massachusetts, November 10 – 14.
"Genetic medicines have made tremendous progress towards precise downregulation of gene expression. However, to extend their reach, we need to bidirectionally control the expression of multiple genes simultaneously," said Thomas McCauley, Ph.D., Chief Scientific Officer of Omega Therapeutics. "We believe that these new data demonstrate the power of our programmable epigenomic mRNA development candidates to control gene expression with unmatched flexibility. To our knowledge, these are the first results to show how site-specific epigenomic modulation can durably upregulate the expression of a master liver regeneration gene. Additionally, a second poster highlights our ability to multiplex gene regulation with a single construct to control a cluster of inflammatory chemokines. These exciting results highlight the progress we have made and possible applications of our approach in multiple liver diseases."
Poster 3444-A: Induction of Hepatocyte Nuclear Factor 4 alpha (HNF4?) using novel epigenomic controllers
Key Findings
- Human cell lines treated with an epigenomic controller (EC) engineered to modulate the epigenetic profile of the P1 promoter of the HFN4? gene, a master regulator of liver development and function, showed strong increases of mRNA and protein levels.
- Upregulation of HFN4? expression following a single EC treatment persisted for ?10 days and induced strong and durable increases in HNF4? mRNA levels in primary human hepatocytes.
- EC-mediated upregulation of HNF4? expression correlated with significantly reduced expression of clinically relevant fibrotic genes in vitro.
- Single ...