Strategic study of atelocollagen-mediated application of myostatin-targeting siRNA for therapeutic use for muscular atrophy diseases

去端肽胶原介导的肌肉生长抑制素靶向 siRNA 用于治疗肌肉萎缩疾病的策略研究

• 批准号: 22890125
• 负责人: KAWAKAMI Emi
• 金额: $ 1.91万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Research Activity Start-up
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-22890125/
• 关键词: 筋ジストロフィー; マイオスタチン; RNAi; 骨格筋; 筋電図; 筋張力

Muscular dystrophy is a severe muscle wasting disorder caused by gene mutations. The disease is lethal, but the treatment of the basic genetic defect has not been established. Recently, many studies have been performed towards establishing an effective treatment for muscular dystrophy.After local application of the Mst-siRNA/ ATCOL complex, masseter muscles were enlarged, while no significant change was observed on the contralateral side. Histological analysis showed that the myofibril sizes of the masseter muscles treated with the Mst-siRNA/ ATCOL complex were larger than those of the control side. The Mst-siRNA/ ATCOL treated muscles were further examined by a real-time PCR analysis, showing a significant down-regulation of Mst gene expression in the treated masseters of both wild type and mCAV-3Tg mice. From EMG records, the amounts of masseter muscle activity in mCAV-3Tg mice were increased by local administration of Mst-siRNA/ ATCOL complex. Furthermore, systemic application of the Mst-siRNA/ ATCOL complex induced considerable recovery of contractile forces for TA muscles in mCAV-3Tg mice.

肌营养不良是一种严重的肌肉萎缩性疾病引起的基因突变。这种疾病是致命的，但基本的遗传缺陷的治疗方法尚未建立。近年来，针对肌营养不良症的有效治疗进行了大量研究，局部应用Mst-siRNA/ ATCOL复合物后，大鼠咬肌增大，而对侧未见明显变化。组织学分析显示，Mst-siRNA/ ATCOL复合物处理的咬肌的肌原纤维尺寸大于对照侧的那些。通过实时PCR分析进一步检查Mst-siRNA/ ATCOL处理的肌肉，显示在野生型和mCAV-3 Tg小鼠的处理的咬肌中Mst基因表达的显著下调。从肌电图记录，在mCAV-3 Tg小鼠咬肌活动量增加的Mst-siRNA/ ATCOL复合物的局部给药。此外，全身应用Mst-siRNA/ ATCOL复合物诱导mCAV-3 Tg小鼠TA肌肉的收缩力显著恢复。

项目成果

Delivery of small interfering RNA with a synthetic collagen poly(Pro-Hyp-Gly) for gene silencing in vitro and in vivo

• DOI: 10.1111/j.1440-169x.2010.01206.x
• 发表时间: 2010-10-01
• 期刊: DEVELOPMENT GROWTH & DIFFERENTIATION
• 影响因子: 2.5
• 作者: Adachi, Taro;Kawakami, Emi;Noji, Sumihare
• 通讯作者: Noji, Sumihare

特殊加工コラーゲンを担体としたマイオスタチンsiRNA投与による骨格筋量調節法の研究

以特殊加工的胶原蛋白为载体，通过肌肉生长抑制素 siRNA 给药进行骨骼肌质量调节方法的研究

• 发表时间: 2010
• 作者: 川上恵実;木内奈央;足立太郎;中村彩花;川合暢彦;田中栄二;野地澄晴
• 通讯作者: 野地澄晴

Atelocollagen-mediated systemic administration of myostatin-targeting siRNA improves muscular atrophy in caveolin-3-deficient mice

• DOI: 10.1111/j.1440-169x.2010.01221.x
• 发表时间: 2011-01-01
• 期刊: DEVELOPMENT GROWTH & DIFFERENTIATION
• 影响因子: 2.5
• 作者: Kawakami, Emi;Kinouchi, Nao;Noji, Sumihare
• 通讯作者: Noji, Sumihare

生体の科学「マイオスタチンの発現抑制による治療」

生物科学“抑制肌肉生长抑制素表达的治疗”

• 发表时间: 2011
• 作者: 川上恵実;他
• 通讯作者: 他

生体の科学「筋ジストロフィーの分子病対から治療へ」

生物科学“从分子发病机制到肌营养不良症的治疗”

• 发表时间: 2011
• 作者: 川上恵実;ら
• 通讯作者: ら