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超声靶向微泡破坏介导基因转染促进胰岛β细胞再生和葡萄糖调节。

Ultrasound-Targeted Microbubble Destruction Mediates Gene Transfection for Beta-Cell Regeneration and Glucose Regulation.

机构信息

Department of Ultrasound and Research Center of Ultrasound in Medicine and Biomedical Engineering, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, China.

Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, 88 Jiefang Road, Shangcheng District, Hangzhou, 310009, China.

出版信息

Small. 2021 Aug;17(31):e2008177. doi: 10.1002/smll.202008177. Epub 2021 Jun 29.

DOI:10.1002/smll.202008177
PMID:34185956
Abstract

Ultrasound-targeted microbubble destruction (UTMD) mediates gene transfection with high biosafety and thus has been promising toward treatment of type 1 diabetes. However, the potential application of UTMD in type 2 diabetes (T2D) is still limited, due to the lack of systematic design and dynamic monitoring. Herein, an efficient gene delivery system is constructed by plasmid deoxyribonucleic acid (DNA) encoding glucagon-like peptide 1 (GLP-1) in ultrasound-induced microbubbles, toward treatment of T2D in macaque. The as designed UTMD afforded enhancement of cell membrane penetration and GLP-1 expression in macaque, which is characterized by ultrasound-guided biopsy to monitor the dynamic process of islet cells for 6 months. Also, improvement of pancreatic beta cell regeneration, and regulation of plasma glucose in macaque with T2D is achieved. The approach would serve as promising alternatives for the treatment of T2D.

摘要

超声靶向微泡破坏(UTMD)介导的基因转染具有很高的生物安全性,因此有望用于治疗 1 型糖尿病。然而,由于缺乏系统的设计和动态监测,UTMD 在 2 型糖尿病(T2D)中的潜在应用仍然有限。在此,通过超声诱导微泡中的质粒脱氧核糖核酸(DNA)编码胰高血糖素样肽 1(GLP-1)构建了一种有效的基因传递系统,用于治疗食蟹猴的 T2D。所设计的 UTMD 增强了食蟹猴的细胞膜穿透和 GLP-1 表达,通过超声引导活检监测胰岛细胞的动态过程长达 6 个月。此外,还实现了 T2D 食蟹猴胰腺 β 细胞再生和血浆葡萄糖水平的调节。该方法将为 T2D 的治疗提供有前途的替代方案。

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