TY - JOUR
T1 - Electrogenetic cellular insulin release for real-time glycemic control in type 1 diabetic mice
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
N1 - Publisher Copyright:
© 2020 American Association for the Advancement of Science. All rights reserved.
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
U2 - 10.1126/science.aau7187
DO - 10.1126/science.aau7187
M3 - 文章
C2 - 32467389
AN - SCOPUS:85085634639
SN - 0036-8075
VL - 368
SP - 993
EP - 1001
JO - Science
JF - Science
IS - 6494
ER -
