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

我们将针对NFKB和ets的诱饵寡脱氧核苷酸（ODN）修饰为带状圆形结构，以增加其系统给药的稳定性。在弹性酶诱导的大鼠动脉瘤模型中腹腔注射带状诱饵ODNs （R-ODNs）。嵌合R-ODN治疗显著抑制主动脉扩张，同时巨噬细胞中几种蛋白酶的分泌减少。相比之下，传统的硫代诱饵ODN未能阻止动脉瘤的形成。此外，我们在小鼠动脉瘤模型中研究了静脉注射改性R-ODN对NFKB的影响。改良的R-ODN治疗显示出减小AAA大小的趋势，进一步改进诱饵策略将为人类AAA提供一种侵入性较小的分子治疗手段。

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.