Scientists Develop a Bioelectronic Device That Can Regulate Genes From Outside the Body

Sounds like science fiction, right?

A team of researchers led by Martin Fussenegger, ETH Professor of Biotechnology and Bioengineering at the Department of Biosystems Science and Engineering in Basel, have published a study which is the first to explore how gene expression can be directly activated and regulated using electrical signals in mice.

The study, published in the journal Science, outlines the researchers’ prototype device being tested in mice, where they established that it works "perfectly". "We've wanted to directly control gene expression using electricity for a long time; now we've finally succeeded," Fussenegger says.

Designer cells are an emerging focal point of synthetic biology, poised with potential to produce or deliver therapeutics essentially on cue. Collectively, the research team have a large amount of experience in creating genetic networks and synthetic implants that are able to respond to certain physiological states in the body, such as varying blood lipid levels or blood sugar levels. Such networks have been demonstrated to respond to biochemical stimuli, in addition to external stimuli – such as light. But what about electricity?

A futuristic bioelectronic device

That was the next challenge. Fussenegger and team have designed a bioelectronic device made up of several components, including a printed circuit board and a capsule containing engineered human β cells, created so that they respond to membrane depolarization by rapidly releasing insulin from intracellular storage vesicles. Connecting these two components is a tiny cable. The bioelectronic device is implanted and a radio signal outside of the body activates the electronics within the device, which subsequently transmits a signal directly to the cells. The signal triggers a charge reversal at the cell membrane, and so calcium ions flow into the cell, and potassium ions flow out. The temporary charge reversal activates the insulin-producing gene, and as a result insulin is transported to the membrane where it is then released.

In this study, the researchers tested their device in a Type 1 diabetes mouse model, implanting it subcutaneously, and found that the electrotriggered vesicular release system could restore normal blood glucose levels in real-time, with insulin levels peaking within 10 minutes.

The researchers posit that, theoretically, the device could be implanted into the body of a diabetic individual and connected to an app on their smartphone. Once the patient eats food and their blood sugar levels begin to rise, they could use the app on their phone to trigger an electrical signal, and a short while afterwards the cells could be triggered to release the required amount of insulin to regulate the individual patient's blood glucose levels.

The internet of the body

Fussenegger believes that there is an array of advantages to the team’s latest development: "Our implant could be connected to the cyber universe," he says. "Doctors or patients could use an app to intervene directly and trigger insulin production, something they could also do remotely over the internet as soon as the implant has transmitted the requisite physiological data."

"A device of this kind would enable people to be fully integrated into the digital world and become part of the Internet of Things – or even the Internet of the Body," Fussenegger says.

It's easy to get excited at the prospect, but the device is novel, and a myriad of considerations must be taken into account before this even gets close to humans.

Firstly, it's well known that electrical devices are at the risk of being hacked. To this end, Fussenegger says: "People already wear pacemakers that are theoretically vulnerable to cyberattacks, but these devices have sufficient protection. That's something we would have to incorporate in our implants, too."

Furthermore, the device interacts with genetics, and, as the advent of technologies such as CRISPR and genome engineering tools have demonstrated, this is not taken lightly from a safety and regulatory point of view. The scientists will need to conduct more research to confirm that no damage is caused to the cells and the genes within those cells, and to determine what the maximum electrical current that can be adopted is.

Finally, in terms of logistics, how will the cells in the implant be replaced? The team's current work suggests that this is something that would need to be done every three weeks. How practical would this be?

References:

Krawcyzk et al. (2020). Electrogenetic cellular insulin release for real-time glycemic control in type 1 diabetic mice. Science. DOI: 10.1126/science.aau7187.