Scientists at ETH Zurich in Switzerland have designed and tested a synthetic gene circuit that responds to beverage concentrations of caffeine.
It achieves this by releasing a glucose control compound used to treat type 2 diabetes.
The researchers inserted the circuit into cells and implanted them into diabetic mice.
They showed that coffee consumption brought down blood glucose levels in line with different doses of caffeine.
Once the caffeine had entered the mice’s bloodstream, it activated the synthetic gene circuit, causing it to release the compound to bring down glucose levels.
The researchers report their findings in a study paper published recently in the journal Nature Communications.
Diabetes burden is growing worldwide
Diabetes is a growing public health problem that affects hundreds of millions of people worldwide.
The epidemic is primarily due to rising rates of type 2 diabetes, a condition that develops when cells lose their ability to employ insulin to convert glucose, or blood sugar, into energy.
In the United States, approximately 23.1 million cases of diabetes have been diagnosed — the vast majority of them type 2. The estimated annual cost of this burden exceeds $245 billion.
But even though treatments have advanced significantly over recent years and can significantly reduce the risk of complications, diabetes is still the seventh leading cause of death in the U.S.
This burden could be reduced if more individuals achieved the treatment targets recommended by their doctors. Experts suggest that we need better “models of care” to tackle the problem.
At present, patients have to monitor blood glucose levels after every meal and promptly respond to any increases with the prescribed treatment.
Synthetic biology and gene circuits
The researchers describe synthetic biology as a “fusion between engineering and biology” that, in recent years, has enabled scientists to devise gene circuits for biomedical use.
Synthetic gene circuits reprogram cells to use their existing machinery in a particular way.
One example of this is the development of “molecular switches” that can tightly control immune cells in a bid to make cancer treatment safer and more precise.
Scientists face a number of challenges when designing synthetic gene circuits. Among these is choosing the right trigger so that the circuit is not activated by mistake and ensuring that the response is limited to that which is required and does not produce side effects.
Caffeine-triggered peptide production
In the paper, the scientists describe how they created “fully synthetic receptors that sense caffeine” at levels equivalent to those present in a typical cup of coffee.
Receptors are proteins that sit on the surface of cells and react only when they encounter a specific molecule, like a unique key inserted into a lock. This act of binding triggers a specific reaction inside the cell.
Here, the trigger is caffeine and the reaction is the production of “synthetic human glucagon-like peptide 1,” which is a compound used in the treatment of type 2 diabetes to bring down blood levels of glucose.
The study authors call the genetic circuit a “caffeine-stimulated advanced regulator (C-STAR).” They tested the C-STAR by inserting it into “designer cells.”
The researchers tested the response of the C-STAR cells to various sources and doses of caffeine in the laboratory, including commercial brands of beverages. They also implanted the cells into mice that were bred to develop type 2 diabetes.
‘Improved glucose control’
In both the cell tests and the mice implanted with C-STAR cells, the presence of caffeine triggered a reversible and dose-dependent change in gene expression.
At first, the team just tested the effect of the trigger by linking it to a “reporter gene” that coded for a protein they could test.
Then the research team replaced the reporter gene with a gene that codes for “an engineered protein clinically licensed” for the treatment of type 2 diabetes, which is the synthetic human glucagon-like peptide 1.
Once triggered, the circuit caused the cells to produce glucagon-like peptide 1. Treated mice showed “substantially improved” glucose control compared with untreated controls.
‘Therapy integrated with lifestyle’
The team suggests that one of the advantages of using caffeine as the trigger is that it is “non-toxic, inexpensive, and only present in specific beverages.”
The new study shows that it is possible to “fine-tune” treatments based on synthetic gene circuits to react to everyday drinks “such as tea and coffee without supplementation of any additional chemicals,” note the authors.
Moreover, “by integrating therapy with lifestyle,” the researchers suggest that the approach could be a way to get patients to comply more readily with treatment regimens, as they conclude:
“Capitalizing on routine cultural habits, therapies based on such systems should seamlessly integrate into people’s lifestyle, and therefore could be a key pillar upon which the new generation of personalized medicine can build.”
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