One shot creates the body’s own weight loss drug factory

What if your body can produce your own weight loss medications that eliminate the need for weekly injections, which can cost hundreds of dollars and usually lead to weight gain when it stops?

Japanese researchers have designed a single genome editing treatment that converts liver cells into biopharmaceutical factories that produce sustained appetite-suppressing hormones for months.

The method, published in Communication Medicine, represents a paradigm shift from traditional genome editing that corrects genetic mutations to create entirely new biological functions. Instead of fixing broken genes, the technology transforms the liver into a pharmaceutical factory.

Engineering Biopharmaceutical Production

The Osaka University team aims to be Atenatide, a GLP-1 receptor agonist that mimics the naturally occurring after hormones. These drugs show a feeling of fullness to the brain and digest slowly, thereby reducing appetite and weight loss. But, like most protein-based drugs, erenetin breaks down rapidly in the body.

“Alternatives to genome editing for many complex and non-genetic diseases are biological drugs, which are essentially injectable proteins,” explains senior author Keii Chiro Suzuki. “These drugs don’t stay in the body for a long time, meaning they usually have to be injected weekly or even daily to maintain consistent treatment levels for the drug.”

The researchers solved the problem by designing an improved version of the Etenatide (called ccexenatide) to continuously secrete. They fuse the drug with a cell “traffic tag” that directs the protein from the cell and adds an enzyme that treats the drug into an active form, once secreted.

Accurate and continuous results

The team used a technique called HITI (the target integral that is not related to homology) to insert the co-glycosaccharide gene directly into the albumin locus, a highly active gene region in hepatocytes. This strategic placement ensures robustness of weight loss compounds, specific to liver production.

This turned out to be amazing. In obese prediabetic mice, single treatment maintained detectable identification levels in the blood for 28 weeks, which was the entire duration of the study. This continuous drug production translates into important metabolic benefits:

• Food intake decreased by 29% compared to untreated obese mice
• Weight loss of 34%, match levels seen in lean control mice
• Improve glucose tolerance and insulin sensitivity
• Standardized blood sugar markers including HBA1C levels

Better than current treatment

Genome editing methods have obvious advantages over conventional drug delivery. Although mice receiving continuous posterior acid through implanted pumps showed benefits only during active treatment, genome-edited animals maintained improvement throughout the study period.

When the researchers removed the drug pump at 8 weeks to simulate treatment interruptions, the control mice quickly recovered their weight and lost their metabolic benefits. However, genome-edited mice continued to produce their own drugs and maintained weight loss.

Digital PCR analysis showed that only about 1% of hepatocytes successfully integrated new genes, but this modest efficiency proved to be sufficient for therapeutic effects. High expression levels of albumin genes compensate for relatively few modified cells.

Security and wider application

Safety analysis showed no obvious hepatotoxicity or off-target genetic effect. This treatment does not interfere with the production of natural hormones—even with continuous secretion, endogenous GLP-1 levels remain normal.

The lipid nanoparticles used by the researchers resemble those in approved therapies to deliver genome editing components specifically to liver cells. This target approach minimizes systemic exposure and potential side effects.

“We hope that our design of one-time genetic treatments can be applied to many diseases that do not have a definite genetic cause,” Suzuki noted. The technology may be possible for other protein-based drugs used to treat inflammatory diseases, autoimmune diseases and metabolic diseases.

What is the future

This approach addresses the fundamental limitations of current biologics – their short half-life requires frequent administration. By converting the body into a drug manufacturing facility, the technology can improve treatment compliance, reduce costs and prevent the rebound effects common when drug production is shut down.

However, questions about long-term safety, optimal dose and patient selection remain. The researchers acknowledge that future studies must evaluate the methods in various obesity models and evaluate the effects on gastric emptying and other physiological functions.

This work brings new possibilities for the treatment of complex diseases without a clear genetic cause – affecting millions of conditions but still beyond the scope of traditional gene therapy. If successfully converted to humans, it could change how we transform chronic disease management from repeated treatments to one-time interventions.

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