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

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

  • Krawczyk K Department of Biosystems Science and Engineering, ETH Zurich, CH-4058 Basel, Switzerland.
  • Xue S Department of Biosystems Science and Engineering, ETH Zurich, CH-4058 Basel, Switzerland.
  • Buchmann P Department of Biosystems Science and Engineering, ETH Zurich, CH-4058 Basel, Switzerland.
  • Charpin-El-Hamri G Département Génie Biologique, Institut Universitaire de Technologie Lyon 1, F-69622 Villeurbanne Cedex, France.
  • Saxena P Department of Biosystems Science and Engineering, ETH Zurich, CH-4058 Basel, Switzerland.
  • Hussherr MD Department of Biosystems Science and Engineering, ETH Zurich, CH-4058 Basel, Switzerland.
  • Shao J Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, People's Republic of China.
  • Ye H Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, People's Republic of China.
  • Xie M Department of Biosystems Science and Engineering, ETH Zurich, CH-4058 Basel, Switzerland.
  • Fussenegger M Department of Biosystems Science and Engineering, ETH Zurich, CH-4058 Basel, Switzerland. fussenegger@bsse.ethz.ch.
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  • 2020-05-30
Published in:
  • Science (New York, N.Y.). - 2020
Animals
Bionics
Calcium Channels, L-Type
Calcium Signaling
Cell Engineering
Diabetes Mellitus, Experimental
Diabetes Mellitus, Type 1
Electric Stimulation
HEK293 Cells
Humans
Insulin Secretion
Insulin-Secreting Cells
Male
Mice
Potassium Channels, Inwardly Rectifying
Prostheses and Implants
Transcription, Genetic
Transgenes
Wireless Technology
English 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.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/295182
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