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

使用具有带状圆形结构的诱饵寡脱氧核苷酸开发动脉瘤的新型治疗方法。

• 批准号: 20590251
• 负责人: MIYAKE Takashi
• 金额: $ 3.08万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590251/
• 关键词: 核酸医薬; 動脈瘤; デコイ

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.

我们将针对NF κ B和ets的诱骗性寡核苷酸（ODN）修饰成带状环状结构，以增加其全身给药的稳定性。在弹性蛋白酶诱导的大鼠动脉瘤模型中进行腹膜内注射带状诱饵ODN（R-ODN）。用嵌合R-ODN治疗显著抑制主动脉扩张，伴随着巨噬细胞分泌的几种蛋白酶的减少。相比之下，传统的硫代磷酸酯诱饵ODN未能防止动脉瘤形成。此外，我们研究了静脉内注射修饰的R-ODN对小鼠动脉瘤模型中NF κ B的影响。用修饰的R-ODN治疗显示出减小AAA大小的趋势。诱饵策略的进一步修改将为人类AAA提供一种侵入性较小的分子治疗手段。

项目成果

Systemic Administration of Ribbon-type Decoy Oligodeoxynucleotide Against Nuclear Factor κB and Ets Prevents Abdominal Aortic Aneurysm in Rat Model

• DOI: 10.1038/mt.2010.208
• 发表时间: 2011-01-01
• 期刊: MOLECULAR THERAPY
• 影响因子: 12.4
• 作者: Miyake, Takashi;Aoki, Motokuni;Morishita, Ryuichi
• 通讯作者: Morishita, Ryuichi

Intra-peritoneal Application of Ribbon-type Decoy Oligodeoxynucleotides against NFkB and ets Prevents Aneurysm Foemation in Rats.

腹膜内应用抗 NFkB 和 ET 的丝带型诱饵寡脱氧核苷酸可预防大鼠动脉瘤形成。

• 发表时间: 2010
• 作者: 三宅隆;et al.
• 通讯作者: et al.

Inhibition of aneurysm development by intra-peritoneal application of ribbon-type decoy oligodeoxynucleotide against nuclear factor-κB and ets in a rat model.

在大鼠模型中腹膜内应用针对核因子-κB 和 ets 的带状诱饵寡脱氧核苷酸抑制动脉瘤的发展。

• 发表时间: 2008
• 作者: 三宅隆;et al.
• 通讯作者: et al.

Intra-peritoneal Application of Ribbon-type Decoy Oligodeoxynucl eotides against NFkB and ets Prevents Aneurysm Foemation in Rats

腹膜内应用抗 NFkB 和 ET 的丝带型诱饵寡脱氧核苷酸可预防大鼠动脉瘤形成

• 发表时间: 2010
• 作者: Miyake T;et al.
• 通讯作者: et al.

核酸医薬を用いた腹部大動脈瘤の低侵襲治療

核酸药物微创治疗腹主动脉瘤

• 发表时间: 2009
• 作者: 三宅隆;他
• 通讯作者: 他