雜志名稱：Nature Communications
影響因子：14.7
文章題目：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
作者單位：
同濟(jì)大學(xué)醫(yī)學(xué)院上海第十人民醫(yī)院
復(fù)旦大學(xué)中山醫(yī)院
同濟(jì)大學(xué)醫(yī)學(xué)院
上海超聲診療工程研究中心
引用YOBIBIO產(chǎn)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.
肥胖是一個(gè)日益嚴(yán)峻的全球健康挑戰(zhàn)，需要有效、可及和創(chuàng)新的治療模式。在這里，我們開(kāi)發(fā)了一個(gè)時(shí)空可控的微針 （MN） 藥物遞送平臺(tái)，用于聲波基因治療以對(duì)抗肥胖。該平臺(tái)將甲氧基聚乙二醇-聚乙烯亞胺 （mPEG-PEI） 修飾的金屬有機(jī)框架 （MOF） 聲敏劑和成簇的規(guī)則間隔短回文重復(fù)序列激活 （CRISPRa）/CRISPRa 解偶聯(lián)蛋白 1 （UCP1） 系統(tǒng)皮內(nèi)輸送到脂肪細(xì)胞�？傮w而言，該治療平臺(tái)能夠?qū)崿F(xiàn)“殲滅”和“對(duì)策”兩大策略：一是通過(guò)聲動(dòng)力療法殺死多余的白色脂肪細(xì)胞，二是通過(guò) CRISPRa-UCP1 系統(tǒng)的可控釋放和聲動(dòng)力效應(yīng)促進(jìn)白色脂肪細(xì)胞褐變。用這種聲波基因療法治療的肥胖雄性小鼠在葡萄糖耐量和胰島素敏感性方面顯示出顯著改善，成功實(shí)現(xiàn)體重減輕并抑制體重反彈。這項(xiàng)研究可能為肥胖和其他代謝疾病的聲索基因治療提供標(biāo)準(zhǔn)治療范式。
