Innovative genome editing approach could be the key to lifelong effective weight management

Weight-loss drugs have surged in popularity, promising rapid results with regular injections. Now, researchers from Japan report a way for the body to make its own weight-loss drugs, doing away with injections in favor of a one-time treatment.

In a study due to be published in Communications Medicine, researchers from The University of Osaka have revealed that a modified genome editing approach to tackle noncommunicable, multifaceted diseases. The approach introduced a new protein-coding gene, rather than attempting to correct a mutation in an existing gene and could be the key to lifelong effective weight management.

Genome editing is a cutting-edge treatment approach that works by correcting genetic mutations that cause disease. However, it is less effective for conditions that aren't caused by a single mutation, like heart disease, diabetes, and obesity. As these are some of the leading causes of mortality, the research aimed to discover how gene therapy can provide therapeutic gain in these diseases.

An alternative to genome editing for many complex and non-genetic diseases is biologic medications, which are essentially injectable proteins. These medications do not stay in the body long, meaning they typically have to be injected weekly, or even daily, to maintain consistent therapeutic levels of the drug."

Keiichiro Suzuki, senior author of the study

To reduce the need for constant injections, the researchers developed an approach combining genome editing with biologics. They introduced a gene that encodes Exenatide, a weight-loss medication that acts as a glucagon-like peptide-1 receptor agonist, into mice with obesity and pre-diabetes. They then monitored Exenatide levels in the blood, as well as weight and food intake, over the next few months.

"The results were very exciting," explains Suzuki. "We found that these genome-edited mice produced high levels of Exenatide that could be detected in blood for several months after introduction of the gene."

Introducing the gene into the mice encouraged the liver cells to continue producing Exenatide, creating a 'reservoir' of the medication in the liver. This reservoir ensured there was a steady flow of Exenatide in the bloodstream, as shown in the research findings.

In addition, the treated mice ate less food and gained less weight than normal mice whose genomes were not edited. Equally, the genome-edited mice being able to produce their own Exenatide improved their glucose metabolism and insulin sensitivity, key factors in controlling diabetes symptoms, without any noticeable side effects.

"We hope that our design of a one-time genetic treatment can be applied to many conditions that do not have exact genetic causes," says Suzuki.

This innovative approach could be an alternative to standard genome editing, which is unable to treat diseases like Type 2 diabetes and chronic inflammatory conditions. Enabling sustained in-body drug production could shorten treatment time, improve treatment adherence, and raise the quality of life for many patients.

Source:
Journal reference:

Hirose, J., et al. (2025). Targeted in vivo gene integration of a secretion-enabled GLP-1 receptor agonist reverses diet-induced non-genetic obesity and pre-diabetes. Communications Medicine. doi.org/10.1038/s43856-025-00959-8.

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