For a solid proof of concept, a team of scientists led by Martin Fussenegger of the Swiss Higher Technical School of Zurich (ETH) developed a system for treating type 2 diabetes in mice by drinking copious amounts of coffee. In fact, when animals drink coffee (or any other caffeinated beverage, such as tea), an artificial genetic system is turned on in cells implanted in mice in the abdominal cavity. This leads to the production of a hormone that increases insulin production, thereby lowering blood sugar levels.
Scientists note that biologists involved in the development of artificial genetic systems have long been looking for such inductors that could trigger artificial genetics. But the previous versions of the inductors had problems. These include antibiotics, which can stimulate drug resistance in bacteria, and to food additives that can have side effects. Caffeine is non-toxic, cheap to manufacture, and only found in certain beverages such as coffee and tea. These drinks are very popular, and more than two billion cups of coffee are drunk every day around the world.
A key component of the system is that protein that can respond to the presence of caffeine in the bloodstream. To do this, the researchers used antibodies produced by the camel's body that can detect caffeine. In the presence of caffeine, this antibody - aCaffVHH - binds to caffeine and then dimerizes. In other words, two aCaffVHHs join together, pinching the caffeine molecule together. The researchers combined half of the protein with one antibody and the other half with a second antibody, then the antibodies can form a complete functional protein when they dimerize. Thus, scientists could only activate this protein with caffeine-induced dimerization.
The most sensitive to caffeine was the system that used the EpoR regulator, which becomes active when it dimerizes and induces a transcription factor called STAT3. Like all transcription factors, STAT3 functions by binding specific bits of DNA to control gene expression.
Scientists engineered a STAT3-binding segment in stem cells that drives a gene that encodes a synthetic human hormone called GLP-1, or glucagon-like peptide-1. This hormone causes the body to produce its own insulin, which in turn lowers blood sugar. Synthetic GLP-1 is considered a potential treatment for type 2 diabetes, in which there is high blood sugar and insufficient insulin production. This disease affects more than 400 million people worldwide.
The researchers packed these GLP-1-producing stem cells into a permeable capsule, and then placed the capsule in the body cavity of mice with type 2 diabetes. After daily doses of coffee in diabetic mice, blood sugar levels were similar to those of healthy mice. They also had much higher blood insulin levels compared to diabetic mice without a GLP-1-producing implant.
It is important to note that daily caffeine intake did not cause problems in the mice, such as an increased heart rate or dangerously low blood sugar. The researchers also noted that decaffeinated drinks did not activate the system.
Scientists are optimistic and even suggest that, with subsequent fine-tuning, they can create personalized systems to match each patient's preferences for caffeine consumption.
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The research results were published in Nature Communications.
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