Individuals seeking to lose weight and manage their blood sugar levels may soon have access to an innovative solution: a single injection that transforms their cells into miniature factories producing a protein similar to the active ingredient found in popular medications like Ozempic, Wegovy, Zepbound, and Mounjaro. This groundbreaking ambition is being pursued by two biotech startups: RenBio, located in New York, and Fractyl Health in Massachusetts. Both companies have successfully completed preliminary tests demonstrating their approaches in mice and are now moving on to larger animal studies involving pigs and monkeys, with the hope of eventually conducting trials in human patients.
With ongoing success and sufficient funding, these biotech innovators aim to bring their gene therapies to the market, although years of research will be needed to confirm their safety and efficacy in humans. Recent advancements in GLP-1 medications, available as both injections and pills, have heralded a new era in obesity treatment. GLP-1, or glucagon-like peptide-1, is a naturally occurring hormone that signals the brain and gut when the body is full, reducing the urge to eat. These new weight loss drugs effectively mimic this hormone's action, enhancing insulin secretion to lower blood sugar levels, while also slowing the digestive process, leading to increased satiety.
According to a recent Gallup report, the percentage of American adults using these medications for weight loss has doubled in less than two years, increasing from 5.8% to 12%. This surge in popularity may have contributed to a slight decrease in the nation’s obesity rate, which fell from 39.9% in 2023 to 37% in 2025. However, the high cost of these medications and the prevalence of side effects, which can include nausea, vomiting, and fatigue, pose challenges for many users. Studies indicate that long-term adherence is necessary for sustained weight loss, yet many individuals are reluctant to remain on these medications indefinitely. A recent study revealed that nearly two-thirds of individuals without diabetes who initiated GLP-1 therapy discontinued use within a year.
In response to these challenges, companies like Fractyl and RenBio are exploring ways to harness the benefits of GLP-1 therapies while minimizing potential downsides. Fractyl is currently presenting its latest findings on a gene therapy known as Rejuva at the annual meeting of the Obesity Society, referred to as ObesityWeek, taking place in Atlanta this week. Meanwhile, RenBio has shared ongoing mouse study results in a preprint paper, which has not yet undergone peer review. They are also set to present updated findings at ObesityWeek.
RenBio's technology, dubbed "Make Your Own," employs a straightforward approach. The researchers utilize a plasmid—a circular piece of DNA—combined with saline solution. DNA, or deoxyribonucleic acid, contains the essential instructions that guide the body’s cellular functions. The researchers have crafted a plasmid containing instructions for producing a GLP-1 receptor agonist protein, similar to the active ingredients in medications like Ozempic and Mounjaro. By injecting this saline solution containing plasmids into muscle tissue and applying short electrical pulses, they facilitate the entry of DNA into muscle cells.
“It works really efficiently. The electrical pulses create temporary pores in the cell membrane, allowing the DNA rings to slip into the cell,” explained Dr. Rachel Liberatore, president and chief scientific officer at RenBio. Once inside, the plasmids migrate to the cell nucleus, where they integrate with the cell's genetic material. When the cell is activated to translate its DNA, the plasmid's code is read, prompting the production of GLP-1 receptor agonist proteins, which are then released into the bloodstream.
Dr. Liberatore emphasized that although RenBio’s therapy utilizes genetic technology, it does not qualify as traditional gene therapy, as it does not attempt to correct defective genes but rather equips cells to produce their own proteins. “The plasmid DNA we are injecting does not interfere with your own chromosomes or DNA, and it is not something that can be passed on to future generations,” she stated. The technology is also being explored for producing other protein therapies, such as antibodies for the Zika virus, with support from organizations like DARPA and BARDA.
In their most productive experiments, mice injected with the plasmids demonstrated an approximate 15% reduction in body weight, a significant improvement compared to control groups. This weight loss was sustained for at least a year post-injection. Although the weight loss plateaued, Dr. Liberatore noted that this is desirable for a long-term therapy, stating, “We were pleased to see that, as continuous weight loss over extended periods could be problematic.” Additionally, glucose tolerance tests indicated improved blood sugar regulation. RenBio envisions that patients may only need injections every year or two to maintain their health.
Fractyl Health is pursuing a different strategy, employing a more traditional gene therapy method that utilizes a small virus called an adeno-associated virus to deliver DNA instructions into cells. This approach carries potential risks, as viral vectors can trigger immune responses that may lead to inflammation or other adverse effects. However, the localized delivery to insulin-producing cells in the pancreas could minimize required dosages, potentially enhancing safety.
“By delivering it locally, we believe that a very low dose of this virus will suffice, which boosts our confidence in its safety for human use,” said Dr. Harith Rajagopalan, co-founder and CEO of Fractyl Health. Early trials in mice and pigs have shown promising results, but the transition to human trials is still a significant hurdle, as many therapies that show efficacy in animals do not translate to humans.
Dr. Donald Kohn, a distinguished professor at UCLA, cautioned that while Fractyl’s approach is promising, much more data is needed before considering human clinical trials. He highlighted concerns regarding the permanence of genetic changes and potential over-expression issues that could arise due to various physiological states.
Fractyl has filed for regulatory approval in the US to initiate human trials, and Dr. Rajagopalan anticipates obtaining human data by 2026. By leveraging the viral capability to deliver DNA into cells, Fractyl aims to enable cells to produce GLP-1, enhancing the body’s ability to regulate blood sugar levels and manage weight effectively.
Fractyl’s gene therapy has shown encouraging results in animal models, with treated obese mice losing approximately 20% of their body weight within three weeks, outperforming existing treatments like semaglutide. Furthermore, normal-weight mice fed high-fat diets maintained stable blood sugar levels, suggesting potential for both treatment and prevention of obesity and diabetes.
Dr. Rajagopalan envisions a future where gene therapy could identify individuals at risk of obesity and offer preventive measures against weight gain. He argues that in an environment overflowing with processed foods, the body struggles to produce adequate GLP-1, and his team sees their gene therapy as a method to help individuals regain control over their appetite and overall health.
“Food is cheaper and more accessible than ever, and our bodies are not equipped to handle it,” Dr. Rajagopalan noted. “The solution may lie in assisting the body to produce more of its own GLP-1.” While the journey to develop these therapies is undoubtedly complex, the potential benefits for weight management and blood sugar control are significant and worthy of pursuit.
