Idera Pharmaceuticals Presents New Preclinical Data on its Gene-silencing Oligonucleotides

“We are very pleased to have observed that the novel structure of GSOs, in which the five-prime end is not accessible, minimizes immune stimulation,” commented Nicola La Monica, Ph.D., Vice President of Biology at Idera Pharmaceuticals. “The immune stimulatory effects of other gene-silencing approaches have resulted in off-target effects that may interfere with the intended mechanism of action or have other unintended consequences. GSOs provide a potential approach for gene-silencing following systemic delivery with reduced off-target effects.”

The data presented are from preclinical studies evaluating the gene silencing activity of GSOs targeted to various messenger RNA targets. The GSOs were administered systemically to mice, without the use of any delivery technology. The GSOs showed significant specific gene-silencing activity as monitored by suppression of targeted RNA and protein. For comparison, a number of antisense sequences were evaluated for in vivo immune activation, as monitored by circulating cytokines. The data showed that GSOs minimized the induction of immune responses compared to antisense oligonucleotides. GSOs are single-stranded oligonucleotides with two exposed 3’-ends and 5’-ends that are not accessible. It has been shown that accessibility of the 5’-ends of oligonucleotides maximizes immune activation.

In preclinical studies, GSOs have inhibited gene expression in vivo without requiring a delivery enhancement technology. Idera has filed multiple patent applications for its GSOs that are pending in many countries around the world.