DNA therapy could deliver long-lasting weight loss treatment

Researchers at The Wistar Institute have developed an experimental DNA-based treatment that could significantly extend the effects of weight loss and diabetes therapies, potentially replacing the need for frequent injections currently required with drugs such as Ozempic and Wegovy. The findings [1] were published in the biotechnology journal Trends in Biotechnology.

The new approach uses a single injection of circular plasmid DNA carrying genetic instructions that enable cells within the body to continuously produce therapeutic molecules over an extended period. In preclinical murine studies, the treatment maintained weight loss and blood glucose control for up to ten times longer than currently available incretin-based therapies.

Current obesity and type 2 diabetes drugs mimic naturally occurring incretin hormones such as GLP-1 and GIP, which help regulate appetite and blood sugar levels. However, because these molecules break down rapidly in the body, patients typically require weekly injections or daily medication to maintain their effects.

The research team engineered specialised DNA constructs known as pLincretins, designed to instruct cells to produce long-acting versions of incretin hormones while resisting rapid breakdown. Using an intramuscular DNA electroporation delivery platform, a single treatment generated detectable therapeutic activity for up to 70 days, producing sustained reductions in body weight and blood glucose levels.

“Instead of delivering a drug that will get cleared by the body, we’re giving cells the instructions to make that drug themselves, and they keep making it,” said Ebony Gary, a research assistant professor in the laboratory of David B. Weiner at The Wistar Institute’s Vaccine and Immunotherapy Center and first author of the study. 

In direct comparisons with semaglutide, the active ingredient used in Ozempic, animals receiving the DNA treatment maintained metabolic improvements long after the study period, while those receiving semaglutide began regaining weight once dosing stopped.

Researchers also used AI-assisted structural modelling to create a second engineered molecule, pSynCretin, designed to activate both GLP-1 and GIP receptors simultaneously. A single dose also delivered sustained weight loss in preclinical testing.

Beyond metabolic disease, the team believes the platform could eventually be adapted to deliver a wide range of long-acting therapeutic proteins for chronic conditions.

More information online

1. Engineering Single-dose Plasmid DNA for Sustained in Vivo Delivery of Designer Incretins, published in Trends in Biotechnology, 2026. Online publication