화학공학소재연구정보센터
Science, Vol.368, No.6494, 993-+, 2020
Electrogenetic cellular insulin release for real-time glycemic control in type 1 diabetic mice
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(v)1.2 and the inwardly rectifying potassium channel K(ir)2.1 to the desired output through endogenous calcium signaling. Focusing on type 1 diabetes, we engineered electrosensitive human beta cells ((Electro)beta cells). Wireless electrical stimulation of (Electro)beta 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.