Using Structuring Interacting RNAs (sxRNAs) as microRNA Inhibitors

DESCRIPTION (provided by applicant): We propose developing a trans-molecular RNA-switch for scientists to negatively affect the activity of endogenous microRNA for use as a molecular tool or therapeutic, an anti-miR. Since the discovery of miRNA, the creation of effective anti-miRs has been important, first to study and verify miRNA interactions, and, secondly, as a therapeutic tool. But, creating an effective anti-miR is not straightforward. At firt glance, one would thing that a strand of RNA in matchinglength and perfectly complementary in sequence would be the ideal anti-miR to fight for the attention of a particular miRNA and effectively neutralize it. However, a perfectly complementary sequence would induce the RISC complex and get cleaved rendering that strategy alone ineffective. While the backbone of the anti-miR can be modified, those modifications do not completely resolve this trade-off in complementariness and cleavage and add hepatoxicity issues to any therapeutic use of anti-miRs. We have