The new gene switch can lead to precise methods of treating metabolic diseases

ETH researchers have developed a new gene switch that can be activated using nitroglycerin -available nitroglycerin slices applied to the skin. One day, scientists want to use this type of switches to trigger cell therapy for various metabolic diseases.

The body regulates its metabolism precisely and constantly, with specialized cells in the pancreas constantly monitor, for example, blood sugar. When this level of blood sugar increases after a meal, the body introduces a signal cascade in motion to bring it.

In people suffering from diabetes, this regulatory mechanism no longer works as it should. That is why people affected by sugar affected are in their blood and have to measure blood sugar levels and inject insulin to regulate it. This is a relatively imprecise approach compared to the mechanism of your own body.

Cell equipment with special functions

Martin Fusenegger is a professor of biotechnology and bioengineering at the Faculty of Biosystems Science and Engineering Eth Zurich in Basel. Bearing in mind the above situation, he and his team have been working on cell therapies for some time. One day, hope is that these therapies will allow you to treat metabolic diseases, such as diabetes individually and thoroughly – and even cure.

But how do these cellular therapies work? First of all, scientists modify human cells, including a network of genes that give cells special skills. These cells are, for example, implanted under the skin, and the network is activated by a specific external stimulus.

The appropriate switch is the key

To this end, scientists have developed various types of switches in recent years. Some can be electrically controlled, others with light, and even using the music of the British rock band Queen (see ETH News).

Scientists in Basel have now developed another variant that they presented on the external website of the magazine.

“For me, this solution is the best gene switch that my group and I have built so far,” says Fusenegger. The reason is that the switch can be started using a long-lasting active component of nitroglycerin and that the means of application-patch patch-is very simple. Appropriate patches are now available for purchase in various sizes in any pharmacy.

Nitroglycerin quickly distracts with patches and skin, where it meets an implant that contains modified human kidney cells.

Network activated by nitric oxide

These cells specifically capture nitroglycerin and have a built -in enzyme that transforms it into nitric oxide (NO), a natural signaling molecule. In the body, it normally causes the expansion of blood vessels, which leads to increased blood flow. It is broken down in a few seconds, and therefore only affects the very located area.

Implanted cells are modified so that none triggers the production and release of the chemical GLP-1 messenger, which in turn increases the release of insulin by beta pancreas cells, and thus regulates blood sugar levels. GLP-1 also triggers satiety, thus reducing food intake.

The new switch takes place only from human ingredients – that is, it does not contain any components of other species.

This is a new and groundbreaking function. In the case of ingredients of other species, there is always a risk of false release, disruptions into your own body processes or immune reactions. “Here we are able to exclude it.”

Martin Fusenegger, professor of biotechnology and bioengineering, Department of Biosystems Science and Engineering, Eth Zurich

All arsenal of switches

Over the past 20 years, Professor ETH has developed various gene switches, some of which react to physical triggers, such as electricity, sound waves or light. Which type has the best chance to implement one day?

“Physical triggers are interesting because we do not have to use molecules that disturb your own body processes,” says the biotechnologist. He explains that electrical signals are ideal for controlling switches and gene networks using portable electronics such as smartphones or smartwatches – and then you can also turn on AI. “That’s why I think that electrogenetic cell therapies have the best chances of implementation. When it comes to chemical switches, I think the new solution is in the pole position, “says Fusenegger.

However, the further development of these cellular therapies based on gene switches is a complex and long process. “The development of cell therapy for market maturity not only occupies decades, but also requires many employees and sufficient resources,” says the researcher. “There is no shortcut.”

Until now, Fusenegger’s work has focused mainly on cellular therapies for diabetes, which is one of the most common metabolic diseases in the world, affecting one in ten people. “This is a model disease with which we work. Basically, however, it is also possible to develop cell therapy for other metabolic, autoimmune or even neurodegenerative diseases – basically everything that requires dynamic regulation. ” According to Fussenegger, many drugs are like a hammer used to blindly hit the problem. “On the other hand, cell therapies solve the problem in a similar way to the body,” he says.