杂志名称：Nature Communications
影响因子：14.7
文章题目：Transdermal microneedle-assisted ultrasound-enhanced CRISPRa system to enable sono-gene therapy for obesity
DOI: https://doi.org/10.1038/s41467-025-56755-4
第一作者：Shaoyue Li, Jifeng Yu, Yuting Shen, Bing Xiong, De Zhao, Weichen Xu, Shen Zhang, Xin Guan, Yunyun Liu, Xuexia Shan, Anqi Zhu, Qi Lyu, Yan Fang, Zitong Chen, Haohao Yin, Liping Sun, Huixiong Xu
作者单位：
同济大学医学院上海第十人民医院
复旦大学中山医院
同济大学医学院
上海超声诊疗工程研究中心
引用YOBIBIO产品：
U96-1511E  Mouse IL-6 ELISA Kit
U96-3112E  Mouse TNF-α ELISA kit
U96-1494E  Mouse IL-1β ELISA Kit

文章摘要：
Obesity, a surging global health challenge, necessitates effective, accessible and innovative therapeutic models. Here we develop a spatiotemporally controllable microneedle (MN) drug delivery platform for sono-gene therapy to fight obesity. The platform delivers the methoxy polyethylene glycol-polyethyleneimine (mPEG-PEI) modified metal-organic frameworks (MOFs) sonosensitizer and the clustered regularly interspaced short palindromic repeats-activating (CRISPRa)/CRISPRa-uncoupling protein 1 (UCP1) system intradermally to adipocytes. Overall, this therapy platform is capable of achieving two major strategies of “annihilation” and “countermeasure”: one is to kill redundant white adipocytes by sonodynamic therapy, and the other is to promote the browning of white adipocytes through the controllable release of CRISPRa-UCP1 system and sonodynamic effect. Obese male mice treated with this sono-gene therapy shows significant ameliorate in glucose tolerance and insulin sensitivity, successfully achieves weight loss and restrains weight rebound. This study may enable a standard treatment paradigm for sono-gene therapy of obesity and other metabolic diseases.

肥胖是一个日益严峻的全球健康挑战，需要有效、可及和创新的治疗模式。在这里，我们开发了一个时空可控的微针 （MN） 药物递送平台，用于声波基因治疗以对抗肥胖。该平台将甲氧基聚乙二醇-聚乙烯亚胺 （mPEG-PEI） 修饰的金属有机框架 （MOF） 声敏剂和成簇的规则间隔短回文重复序列激活 （CRISPRa）/CRISPRa 解偶联蛋白 1 （UCP1） 系统皮内输送到脂肪细胞。总体而言，该治疗平台能够实现“歼灭”和“对策”两大策略：一是通过声动力疗法杀死多余的白色脂肪细胞，二是通过 CRISPRa-UCP1 系统的可控释放和声动力效应促进白色脂肪细胞褐变。用这种声波基因疗法治疗的肥胖雄性小鼠在葡萄糖耐量和胰岛素敏感性方面显示出显着改善，成功实现体重减轻并抑制体重反弹。这项研究可能为肥胖和其他代谢疾病的声索基因治疗提供标准治疗范式。