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Electrogenetics – Shaping Electrogenetic Interfaces for Closed-Loop Voltage-Controlled Gene Expression

Periodic Reporting for period 1 - ElectroGene (Electrogenetics – Shaping Electrogenetic Interfaces for Closed-Loop Voltage-Controlled Gene Expression)

Reporting period: 2018-11-01 to 2020-04-30

Physical objects equipped with electronic sensors and machine-learning software are increasingly exchanging data over the internet of things to collaborate and shape our future. With their molecular structure and analog metabolic control circuits taking generations to upgrade by evolution, living systems including humans are incompatible with the digital electronic world and the internet of things. Indeed, smart wearable devices profiling our habits and fitness day and night are impacting our behavior but for lack of compatibility, they have no access to control our genes and metabolism. However, despite the differences between the biologic and electronic worlds their information processing and control share some basic principles. Biological systems use ion gradients across insulating cell membranes and protein-receptor interactions to propagate analog signals, while electronic devices utilize electrons flowing through metal wires to transfer digital information. Also, biological systems can use airborne volatile molecules to communicate, while electronic systems can employ wireless broadcasting. Furthermore, single cells in a multicellular organism can simultaneously process an enormous amount of analog metabolic information in parallel at slow speed, whereas central processing units in electronic devices process digital information sequentially at enormous speed, but parallel processing requires a multi-core architecture in combination with hyper-threading technology. With the advent of the internet of things, the complexity of the digital world may be approaching that of biological systems, and electrogenetic interfaces to manage information transfer between the biological and electronic worlds may lead to novel strategies for diagnosis, treatment and prevention of diseases.
We have designed the first bioelectronic interface that uses wireless-powered electrical stimulation of human cells to promote the release of insulin. The human cells were genetically engineered to respond to electrically induced membrane depolarization by rapidly releasing insulin from intracellular storage vesicles. A bioelectronic device that incorporates the cells can be wirelessly triggered by a field generator. When subcutaneously implanted in diabetics mice, the device could be triggered to restore normal blood glucose levels. Bioelectronic devices with electrogenetic interfaces will create an internet of the body and advance the integration of human metabolism with the internet of things. This will enable unprecedented therapeutic opportunities for currently uncurable disease such as Diabetes that will soon be affecting over 10 percent of the world’s population.
ElectroGene will pioneer and put into practice a direct interface between the electronic and genetic worlds. This will enable closed-loop control between electronic devices and human metabolism and create an internet of the body as well as connect human metabolism to the internet of the body. Thus, ElectroGene will provide novel options for the treatment of severe medical conditions.
Electrogenetic Implant (Bottom View)
Vesicular Secretion of Electrogenetic Beta Cells
Apple Watch-controlled diabetic mouse
Electrogenetic Implant (Top View)
Smart Watch-Controlled Gene Expression
Electrogenetic Gene Switches