MRG-001 down-regulates pathways associated with inflammation and allograft rejection
RNA sequencing transcriptome studies of peripheral blood mononuclear cells (PBMC) showed no change in gene expression at different time points in the placebo treatment group over the measured 48-h period, which spans one injection cycle. Significant differences in gene expression between placebo and 0.01 mL/kg MRG-001 or 0.02 mL/kg MRG-001 injection were observed (Regulated molecular pathways by MRG-001RNA sequencing transcriptome studies of PBMCs were performed at different time points following a single dose SC injection of saline (placebo) or MRG-001.(A) GSEA for interpreting gene expression profiles revealed 17, 24 and 19 down-regulated pathways at 8, 12, and 24 h after administration of 0.01 mL/kg MRG-001. A total of 31 down-regulated pathways were recognized and summarized in a Venn diagram.(B) GSEA showed 4, 9, 5, and 8 down-regulated pathways at 8, 12, 24, and 48 h, and 1 up-regulated pathway at 8, 24, and 48 h after administration of 0.02 mL/kg MRG-001. A total of 14 down-regulated and 2 up-regulated pathways were recognized, and down-regulated pathways were summarized in a Venn diagram.Considering the diversity of testing subjects, we have also compared gene expression at different time points to pre-dose gene expression. Compared with the pre-dose, 654 down-regulated genes and 1,038 up-regulated genes at 8 h, 630 down-regulated genes and 225 up-regulated genes at 12 h, 199 down-regulated genes and 9 up-regulated genes at 24 h, and 1 up-regulated gene at 48 h were identified in the mid-dose group (Venn diagram analysis of common down-regulated pathways between MRG-001 versus placebo and MRG-001 versus pre-dose revealed 27 common down-regulated pathways in the mid-dose group and 4 down-regulated pathways in the high-dose group (