Development of novel therapeutic approach for aneurysm using decoy oligodeoxynucleotide with a ribbon-shaped circular structure.

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We modified decoy oligodeoxynucleotide (ODN) against NFKB and ets, to a ribbon-shaped circular structure, to increase its stability for systemic administration. Intraperitoneal administration of ribbon-type decoy ODNs (R-ODNs) was performed in an elastase-induced rat aneurysm model. Treatment with chimeric R-ODN significantly inhibited aortic dilatation accompanied by a reduction of secretion of several proteases from macrophages. In contrast, conventional phosphorothioate decoy ODN failed to prevent aneurysm formation. In addition, we investigated the effect of intravenous injection of modified R-ODN against NFKB in a mouse aneurysm model. Treatment with modified R-ODN showed a tendency to decrease the size of AAA. Further modification of the decoy strategy would provide a means of less invasive molecular therapy for human AAA.