DNA-based GLP-1 delivery via MYO Technology

Current GLP-1 receptor agonists like tirzepatide and semaglutide require weekly injections. Stop the injections, and weight tends to come back. The SURMOUNT-4 trial showed that people who discontinued tirzepatide regained roughly 14% of the weight they had lost within a year^[1]. That pattern is one reason researchers are interested in longer-acting delivery methods. A new study published in Molecular Therapy: Nucleic Acids tested one such method in mice, using plasmid DNA and electroporation to make muscle cells produce GLP-1 on their own^[2].

What the researchers did

The team, led by Linda Sasset and Rachel Liberatore at RenBio Inc. (with collaborators at Louisiana State University), used a platform called MYO Technology. MYO stands for "Make Your Own." The idea is straightforward: inject plasmid DNA, a small ring of synthetic DNA encoding a therapeutic protein, into muscle tissue. Then apply brief electrical pulses (electroporation) to open temporary pores in muscle cell membranes, allowing the DNA to enter. Once inside, the muscle cells read the DNA instructions and begin producing and secreting the encoded protein into the bloodstream^[2].

The plasmid DNA does not integrate into the cell's own chromosomes. It sits separately in the nucleus, which means it is not heritable and does not alter the host genome. This distinguishes MYO from traditional gene therapies that use viral vectors to insert DNA directly into chromosomes.

The constructs they tested

The researchers tested several variants of GLP-1-encoding plasmids in diet-induced obese mice (n=5 per group). The constructs included native GLP-1, a GLP-1 fused to a mouse IgG1 Fc domain (to extend its half-life in circulation), and a version that added Angiopep-2, a peptide designed to help the protein cross the blood-brain barrier^[2]. That last variant matters because GLP-1's appetite-suppressing effects are thought to depend partly on signalling in the brain, and getting more of the protein past the blood-brain barrier could, in theory, improve efficacy.

What they found

Mice that received MYO-delivered GLP-1 constructs lost approximately 15% of their body weight compared to placebo-treated controls. The weight loss was sustained for over one year after a single administration^[2]. Glucose tolerance also improved, with treated mice showing better blood sugar regulation in glucose tolerance tests at multiple time points (weeks 2, 6, 8, and 10). Cumulative food intake was reduced in the treated groups.

The Angiopep-2-modified construct, the one engineered to cross the blood-brain barrier, performed better than the simpler GLP-1-Fc fusion. The researchers described this enhancement as "markedly improved efficacy"^[2]. In vitro potency assays indicated that the constructs activated GLP-1 receptors at levels comparable to semaglutide.

Why this is interesting

The durability finding is the headline. Current injectable GLP-1 receptor agonists have half-lives measured in days. They require weekly dosing, and stopping them leads to weight regain. SURMOUNT-4 documented this clearly for tirzepatide: participants who switched to placebo at 36 weeks regained weight, though they remained 9.5% below their starting weight at 88 weeks^[1]. If a single injection could maintain GLP-1 signalling for a year or more, the adherence problem and the regain problem both change shape.

RenBio is not alone in this space. Fractyl Health is working on a viral-vector-based gene therapy approach to sustained GLP-1 production. A separate group published a lipid-nanoparticle-based DNA delivery platform (the Prometheus system) in the same journal in late 2025. The race to move beyond weekly injections is real, even if no approach has reached human trials yet.

What this does not tell us

Several things. First, this is a mouse study. Five mice per group. Diet-induced obese mice are a standard preclinical model, but they do not predict human outcomes with any precision. The gap between mouse and human results in obesity research has been wide and consistent.

Second, there is no safety data beyond the observation that the mice survived and lost weight. Long-term effects of sustained, unregulated GLP-1 production from muscle cells, effects on the gastrointestinal tract, the pancreas, thyroid tissue, have not been characterised. With injectable GLP-1 drugs, a clinician can stop or adjust the dose. A plasmid expressing protein for a year cannot be easily turned off.

Third, the study comes from RenBio, the company that developed MYO Technology. All of the listed authors are affiliated with RenBio or collaborating institutions funded by the programme. The work was supported by DARPA, BARDA, and the Wellcome Trust, which is notable funding, but the conflict of interest is worth flagging.

Fourth, even the mouse results raise questions. In mice kept on a high-fat diet, some GLP-1 constructs showed weight-loss effects that were strongest in the first few weeks and then plateaued. Whether the plateau reflects stable, therapeutic-level GLP-1 production or a waning effect is not clear from the published data.

Where things stand

MYO Technology is preclinical. RenBio has stated an aspiration to begin human testing, but no IND filing has been publicly disclosed as of this writing. The company presented earlier versions of this data at ObesityWeek and as a bioRxiv preprint before the peer-reviewed publication in Molecular Therapy: Nucleic Acids.

For now, the approved GLP-1 and dual-agonist drugs (semaglutide, tirzepatide, and eventually their successors) remain the only options with human efficacy and safety data. The gene-therapy approach is a research direction, not a treatment option. If you are considering GLP-1-based therapy for weight management, consult a healthcare provider about the options that have actually been through human trials.