ACCORDO DI COLLABORAZIONE SCIENTIFICA EX ART. 15 L. 241/1990 - Antagomirs/agomirs in vasculitides: a novel scenario in personalized medicine – MIRNAVASC

Our previous omics data on patients with Behçet's syndrome (BS) (1), along with a growing number of articles concerning vascular and autoimmune diseases, have shown the potential role of circulating microRNAs (ci-miRNAs) both as noninvasive biomarkers for the diagnosis of these diseases and for the identification of ongoing pathogenetic mechanisms (2). Specifically, our research group identified three ci-microRNAs (miRNAs) up-regulated in patients with BS (a rare systemic vasculitis) compared with the general population, suggesting their potential etiopathogenetic role in vascular manifestations (1). Indeed, evidence from the literature suggests that, at the endothelial level, these ci-miRNAs are directly involved in mechanisms of leukocyte perivascular activation and infiltration, production of reactive oxygen species, as well as modulation of factors involved in the coagulation cascade (2). Several RNA-targeting therapeutic agents have been developed and some of them are already successfully used in the clinical setting (i.e. siRNA based drug Inclisiran) (3). Developing tools capable of modulating deregulated miRNAs levels at the endothelial level, influencing their activity as modulators of gene expression (namely AntagomiRs and AgomiRs), may therefore represent a new frontier in the targeted therapy of vasculitides (4). Vascular Inflammatory diseases, indeed pose significant challenges in treatment due to their complex pathophysiology and the need for targeted drug delivery (5). Endothelial cells play a crucial role in inflammation by initiating and perpetuating the inflammatory response. Targeting these cells can be an effective strategy for localized treatment while minimizing systemic side effects. We already identified 3 AntagomiRs sequences based on the three upregulated ci-miRNAs found in BS (1) and validated their effect in an in vitro endothelial model. With this project, we therefore plan to extend this experimental approach to other types of vasculitis.