Silencing Myostatin Using In Vivo Self-Assembled siRNA Protects Against Cancer- and Dexamethasone-Induced Muscle Atrophy.

IF 9.6 2区 医学 Q1 ENGINEERING, BIOMEDICAL
Xin Yin, Azhar Anwar, Jiehao Chen, Qinghao Sun, Likun Zhou, Jie Tang, Jingwei Guo, Linbo Yan, Yongci Chen, Feng Yin, Chen-Yu Zhang, Zigang Li, Jizheng Ma, Liyuan Sheng, Xi Chen
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引用次数: 0

Abstract

Maintaining skeletal muscle mass is crucial for health, as muscle atrophy caused by drugs, cancer, or aging poses serious risks. However, there are few effective pharmacological interventions targeting muscle atrophy, highlighting the need for new therapeutic strategies. In this study, in vivo self-assembled siRNA is designed to silence myostatin (MSTN), a key regulator of muscle growth and atrophy, aiming to prevent muscle atrophy. Using synthetic constructs and the host liver as a scaffold, the assembly of MSTN-siRNA is guided into muscle-specific peptide MSP-tagged small extracellular vesicles (sEVs). These MSP-tagged sEVs selectively deliver MSTN-siRNA to muscle tissue. Treatment significantly reduces MSTN protein levels in skeletal muscle, promotes muscle mass gain in healthy mice, and protectes skeletal muscles from atrophy in cancer- and dexamethasone-induced muscle atrophy models. Notably, the sEV-encapsulated MSTN-siRNA is produced in a nontoxic, nonimmunogenic, and biocompatible manner. This study offers a promising therapeutic approach for muscle atrophy, addressing a key gap in current treatment options and potentially improving outcomes for patients with muscle-wasting conditions.

使用体内自组装siRNA沉默肌肉生长抑制素可预防癌症和地塞米松诱导的肌肉萎缩。
保持骨骼肌质量对健康至关重要,因为由药物、癌症或衰老引起的肌肉萎缩会带来严重的风险。然而,很少有有效的药物干预针对肌肉萎缩,突出需要新的治疗策略。在本研究中,体内自组装siRNA被设计为沉默肌肉生长和萎缩的关键调节因子肌肉生长抑制素(MSTN),以防止肌肉萎缩。利用合成构建物和宿主肝脏作为支架,MSTN-siRNA的组装被引导到肌肉特异性肽msp标记的小细胞外囊泡(sev)中。这些msp标记的sev选择性地将MSTN-siRNA传递到肌肉组织。治疗可显著降低骨骼肌中的MSTN蛋白水平,促进健康小鼠的肌肉质量增加,并在癌症和地塞米松诱导的肌肉萎缩模型中保护骨骼肌免受萎缩。值得注意的是,sev封装的MSTN-siRNA是以无毒、非免疫原性和生物相容性的方式生产的。这项研究为肌肉萎缩提供了一种有希望的治疗方法,解决了当前治疗方案中的关键空白,并有可能改善肌肉萎缩患者的预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Advanced Healthcare Materials
Advanced Healthcare Materials 工程技术-生物材料
CiteScore
14.40
自引率
3.00%
发文量
600
审稿时长
1.8 months
期刊介绍: Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.
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