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

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

doi:10.1126/science.aau7187

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

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

^*此作品的通讯作者

生命科学学院

Department of Biosystems Science and Engineering
Swiss Federal Institute of Technology Zurich
East China Normal University
Département Génie Biologique
Universite Claude Bernard Lyon 1
Key Laboratory of Growth Regulation and Transformation Research of Zheijang Province
Westlake University
Faculty of Science
University of Basel

科研成果: 期刊稿件 › 文章 › 同行评审

189 引用（Scopus）

摘要

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 Ca_V1.2 and the inwardly rectifying potassium channel K_ir2.1 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.

源语言	英语
页（从-至）	993-1001
页数	9
期刊	Science
卷	368
期	6494
DOI	https://doi.org/10.1126/science.aau7187
出版状态	已出版 - 29 5月 2020

联合国可持续发展目标

此成果有助于实现下列可持续发展目标：

可持续发展目标 3 良好健康与福祉

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10.1126/science.aau7187

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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.",

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AU - Krawczyk, Krzysztof

AU - Xue, Shuai

AU - Buchmann, Peter

AU - Charpin-El-Hamri, Ghislaine

AU - Saxena, Pratik

AU - Hussherr, Marie Didiée

AU - Shao, Jiawei

AU - Ye, Haifeng

AU - Xie, Mingqi

AU - Fussenegger, Martin

PY - 2020/5/29

Y1 - 2020/5/29

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85085634639

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

摘要

联合国可持续发展目标

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