Swiss scientists have been able to introduce genetic modifications into human cells, thanks to which certain genes can be selectively turned on using a weak current. The concept was also confirmed in experiments on animals, starting the production of insulin in them by simply pressing a switch. Authors whose article published In the magazine Nature Metabolismhope that their development will help in the creation of medical implants for gene therapy.
Indeed, physicians and patients today are increasingly resorting to the use of compact electronic implants that help monitor heartbeat or blood glucose levels. Devices that actively correct the state of the body are much rarer, and there is still no one that would help in gene therapy – the newest approach to the treatment of diseases by making point changes in the genome of certain somatic cells.
The problem is that genetics and electronics are very far from each other, and the regulation of gene activity is carried out by biochemical signals and tools. Filling the gap between them can be a concept developed by the team of Martin Fussenegger (Martin Fussenegger) from the Swiss Federal Institute of Technology Zurich (ETH Zurich), a technique that the authors called DART (DC-Actuated Regulation Technology, “Direct Current Regulation Technology (Genes)”) .
The system relies on the fact that a weak current brings free electrons into the cell, which in turn leads to an increase in the concentration of reactive oxygen species (ROS), such as peroxide. The cell already has a range of proteins capable of serving as natural scavengers for such radicals, including BUY1, which is involved in tumor suppression. Upon noticing the accumulation of reactive oxygen, KEAP1 releases the NRF2 signaling protein, which enters the cell nucleus and triggers a number of antioxidant and anti-inflammatory mechanisms.
Early experiments showed that low (4.5 volts) direct current did not create enough ROS to activate the KEAP1/NRF2 system. Therefore, scientists modified cells by introducing additional KEAP1 / NRF2 genes into them, as well as changing promoters – sections of DNA that trigger the work of a particular gene – that are affected by NRF2. Such cells “in vitro” already responded to the action of the current, including the insulin gene, which was controlled by the appropriate promoters.
GM cells in laboratory mice were activated via electrodes connected to three conventional AA batteries / ©Huang et al., 2023
The efficiency of DART technology was also confirmed by the following experiments on laboratory animals. The scientists took a model line of type 1 diabetes mice, encapsulated insulin-producing GM cells, and injected them into rodents. Cells were stimulated with electric current of different strength and duration, monitoring the concentration of glucose in the blood of animals.
As a result, the researchers found that the synthesis of insulin (and, as a result, the level of sugar that controls this hormone) correlated with the strength and time of switching on the “gene-electrical” DART interface. In fact, several of these inclusions produced an effect similar to the several injections of insulin per day that are required by many diabetics today. Perhaps in the future, gene therapy supplemented with DART implants will save them from this painful procedure. It will be enough to have a glucose sensor, GM cells and an ordinary battery, which will “turn on” their genes with electricity.
2023-08-01 09:23:33
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