Modern weight-loss medicines have helped millions of people manage obesity and type 2 diabetes, yet they come with one ongoing challenge.
Most patients must continue taking regular injections or tablets to maintain the benefits. Once treatment ends, appetite often returns, blood sugar rises, and lost weight may gradually come back.
Researchers at The Wistar Institute are exploring a very different solution. Instead of giving patients the medicine every week, they want the body to produce the medicine itself for an extended period after a single treatment. Their findings were published in Trends in Biotechnology.
The new strategy uses a harmless circular piece of DNA known as a plasmid. The DNA carries instructions for making proteins that behave like the natural hormones GLP-1 and GIP, which help control hunger and blood sugar.
After the DNA is injected into muscle, doctors use a brief electrical pulse to help nearby cells absorb the instructions. Those cells then begin producing the therapeutic proteins for an extended time.
This technology was not developed from scratch. The research team had already shown in earlier human studies that similar DNA instructions could help the body make protective antibodies for well over a year. They wondered whether the same idea could solve one of the biggest limitations of current obesity medicines—the need for repeated dosing.
To test the idea, the scientists engineered DNA constructs called pLincretins. These instructions also included an added antibody fragment that slowed the breakdown of the newly produced proteins.
When tested in diabetic mice, one treatment maintained detectable hormone production for around 70 days. During this period the animals experienced sustained reductions in body weight and improved blood glucose control.
The team also directly compared the technology with semaglutide, the medicine used in Ozempic. While semaglutide worked well during active treatment, the animals began regaining weight after dosing stopped. Animals receiving the DNA instructions maintained the improvements because their own cells continued making the therapeutic proteins.
The scientists later designed an entirely new hybrid protein called pSynCretin using artificial intelligence and protein engineering. It combined important features from several incretin hormones and medicines into one molecule capable of activating both GLP-1 and GIP pathways. This experimental treatment also produced lasting weight reduction in mice.
Beyond obesity and diabetes, researchers are becoming increasingly interested in the unexpected health effects of incretin therapies. Patients taking these medicines sometimes experience improvements in inflammatory conditions such as psoriasis and arthritis.
The team is now investigating whether these proteins may influence the immune system or even affect cancer biology.
The same DNA platform might also be adapted to deliver many other therapeutic proteins for chronic diseases that currently require repeated injections. Instead of repeatedly supplying medicines from outside the body, future treatments could encourage the body to manufacture them for months.
Despite the promise, these findings should be viewed with caution. The research remains preclinical, meaning it has only been tested in animal models. Human clinical trials are essential before doctors know whether the treatment is safe, durable, affordable, and effective for patients.
The research was published in Trends in Biotechnology.
The greatest strength of this study is its creative delivery technology, which may overcome one of the biggest weaknesses of current GLP-1 medicines. Rather than improving the drug itself, the researchers redesigned how the medicine reaches the body.
However, animal success does not guarantee human success, and many questions remain regarding long-term safety and control of protein production. Overall, this research represents an important proof of concept that could eventually transform how many chronic diseases are treated.
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Source: The Wistar Institute.
