Research Article

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

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Science  29 May 2020:
Vol. 368, Issue 6494, pp. 993-1001
DOI: 10.1126/science.aau7187

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Electronic control of designer cells

There is increasing interest in using designer cells to produce or deliver therapeutics. Achieving direct communication between such cells and electronic devices would allow precise control of therapies. Krawczyk et al. describe a bioelectronic interface that uses wireless-powered electrical stimulation of cells to promote the release of insulin (see the Perspective by Brier and Dordick). The authors engineered human β cells to respond to membrane depolarization by rapidly releasing insulin from intracellular storage vesicles. A bioelectronic device that incorporates the cells can be wirelessly triggered by an external field generator. When subcutaneously implanted in type 1 diabetic mice, the device could be triggered to restore normal blood glucose levels.

Science, this issue p. 993; see also p. 936

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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