Abstract
Abstract Many RNA-based therapeutic oligomer backbone chemistries will elicit undesirable immunological response through a number of pathways. Additionally, it has been shown that certain sequences can also elicit cellular pro-inflammatory responses in the form cytokine and chemokines production. For example, non-methylated CpG DNA motifs are considered pathogen-associated molecular patterns (PAMPS) due to their abundance in microbial genomes and their recognition by TLR-9 receptors. Some synthetic oligonucleotides, containing modified backbone or other synthetic nucleotide motifs, will still retain potent immunostimulatory activity which may be inappropriate within the desired therapeutic effect. The purpose of this study was to look in vitro for immune activation resulting from exposure to optimized CpG sequences incorporated into the phosphorodiamidate morpholino oligomer (PMO) chemistry. Human and murine dendritic cells (DCs) were treated with varying concentration of PMO and culture media was assayed by multiplex cytokine and chemokine detection platform for simultaneous detection of multiple analytes. There was no evidence for a sequence- or chemistry-specific activation of the DCs indicating that PMO do not provide an innate stimulus to the immune system.
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