Electricity used to control human gene expression

Swiss scientists have engineered human cells to respond to an electrical current, which could pave the way for the development of wearable medical devices.

The findings, published in Nature Metabolism, demonstrated that an 'electrogenetic' interface can be used to treat a mouse model of type 1 diabetes.

This technology, referred to as the 'direct current (DC)-actuated regulation technology,' or DART, is an 'interface between the electrical world and the genetic world' according to senior author Professor Martin Fussenegger from the Swiss Federal Institute of Technology, Zurich. He and his co-authors described the findings as 'a leap forward, representing the missing link that will enable wearables to control genes in the not-so-distant future'.

In this experiment, the bioengineered cells were implanted into an experimental type 1 diabetes mouse model, and the electrogenetic interface was used to activate the production of insulin, a key hormone in regulation of blood sugar, leading to restoration of its normal levels in the bloodstream.

DART works by activating a chain reaction: when an electric current is applied to cells, a naturally occurring molecular oxygen form called reactive oxygen species (ROS) is generated. ROS can potentially damage cells, and so its presence causes activation of a gene that makes an antioxidant, which in turn deactivates ROS.

The researchers used this natural feedback mechanism, and inserted a therapeutic gene (in this case, one to make insulin) with the same promoter that the gene that makes the antioxidant has. Thus, when the electrical current is applied to the cells, the inserted gene is expressed and insulin is produced.

They were able to show that implanting bioengineered human cells containing these genes below the skin of mice with high blood sugar, and then activating them with a battery and acupuncture needles caused insulin release and blood sugar levels to drop.

The researchers hope this alternative approach to traditional diabetes treatments has the potential to drastically simplify the management of blood glucose levels by eliminating the need for multiple daily insulin injections. However, they acknowledge that before DART could be translated into clinical practice, further research and clinical trials are needed to evaluate the safety and effectiveness of this approach in humans.

A potential advantage of the technique is that it 'can use normal batteries and lower voltages that are compatible with implantable devices,' as Dr Rodrigo Ledesma-Amaro, a synthetic biologist at Imperial College London who was not involved in the study, told Nature News.

The technique is not limited to diabetes, and in principle could be used to produce other molecules, including other hormones.