Omega presents new preclinical data on pre-transcriptional control of genes

Omega Therapeutics announced new preclinical data showcasing simultaneous and coordinated pre-transcriptional control of multiple genes co-located in an insulated genomic domain, IGD, by a single epigenomic controller, EC, at the 11th International mRNA Health Conference taking place in Berlin, Germany, October 31 – November 2, 2023. “These new preclinical data show that, through deep understanding of disease biology and genomic architecture, our OMEGA platform is able to design a programmable mRNA candidate capable of multiplexing to pre-transcriptionally control the expression of multiple genes in preclinical models,” said Thomas McCauley, Ph.D., Chief Scientific Officer of Omega Therapeutics. “By targeting a genomic locus containing a cluster of cytokine genes, we can precisely modulate immune activity to elicit a meaningful anti-inflammatory response. The potential applications of this strategy extend beyond any single disease and highlight the broad potential of precision epigenomic control.” Key Findings: Treatment of human lung fibroblasts with CXCL1-8-targeting ECs correlated with corresponding decrease in gene expression of multiple CXCL chemokines; EC-induced changes in the epigenetic profiles of the CXCL1-8 genes were associated with decreased binding of NF-kB; Human lung fibroblasts treated with a single CXCL-EC engineered to modulate the epigenetic profiles of the CXCL1-8 gene cluster showed downregulation of both mRNA and protein levels of CXCL1, 2 and 8 ; Cells treated with a CXCL-EC showed decreased ability to support neutrophil migration in vitro; In a mouse model of lung inflammation, single administration of a mouse surrogate CXCL-EC resulted in decreased recruitment of neutrophils and B and T cells into bronchoalveolar fluid