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科学家在1型糖尿病小鼠中实现电遗传细胞的胰岛素释放
作者:小柯机器人 发布时间:2020/5/30 20:03:23

瑞士苏黎世联邦理工学院Martin Fussenegger研究团队在1型糖尿病小鼠中实现电遗传细胞的胰岛素释放。相关论文于2020年5月29日发表在《科学》杂志上。

研究人员提出了一种无辅因子的生物电子界面,该界面直接将人体细胞的无线电刺激与人工合成启动子驱动的转基因表达或从囊泡贮藏库快速分泌组成型表达的蛋白质药物联系起来。通过将L型电压门控通道CaV1.2和向内整流钾通道Kir2.1的异位表达通过内源性钙信号传导耦合到所需的输出,从而可以实现电遗传控制。
 
针对1型糖尿病,研究人员设计了电敏感的人β细胞(Electroβ细胞)。生物电子设备内Electroβ细胞的无线电刺激提供了对囊泡胰岛素释放的实时控制;胰岛素水平可在10分钟内达到峰值。当皮下植入时,这种电触发的囊泡释放系统可恢复1型糖尿病小鼠的正常血糖。
 
据了解,用于远程控制医疗干预的复杂设备需要一个电遗传界面,这种界面使用数字电子输入来直接编程细胞行为。
 
附:英文原文

Title: Electrogenetic cellular insulin release for real-time glycemic control in type 1 diabetic mice

Author: Krzysztof Krawczyk, Shuai Xue, Peter Buchmann, Ghislaine Charpin-El-Hamri, Pratik Saxena, Marie-Didiée Hussherr, Jiawei Shao, Haifeng Ye, Mingqi Xie, Martin Fussenegger

Issue&Volume: 2020/05/29

Abstract: Sophisticated devices for remote-controlled medical interventions require an electrogenetic interface that uses digital electronic input to directly program cellular behavior. We present a cofactor-free bioelectronic interface that directly links wireless-powered electrical stimulation of human cells to either synthetic promoter–driven transgene expression or rapid secretion of constitutively expressed protein therapeutics from vesicular stores. Electrogenetic control was achieved by coupling ectopic expression of the L-type voltage-gated channel CaV1.2 and the inwardly rectifying potassium channel Kir2.1 to the desired output through endogenous calcium signaling. Focusing on type 1 diabetes, we engineered electrosensitive human β cells (Electroβ cells). Wireless electrical stimulation of Electroβ cells inside a custom-built bioelectronic device provided real-time control of vesicular insulin release; insulin levels peaked within 10 minutes. When subcutaneously implanted, this electrotriggered vesicular release system restored normoglycemia in type 1 diabetic mice.

DOI: 10.1126/science.aau7187

Source: https://science.sciencemag.org/content/368/6494/993

期刊信息
Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037