Single‑Shot GLP‑1 Gene Therapies: Could One Injection Replace Ozempic?

Biotechs race to turn patients' cells into GLP‑1 protein factories

Two startups—RenBio (New York) and Fractyl Health (Massachusetts)—are developing gene‑based approaches that aim to make a patient’s own cells produce GLP‑1, the active protein in widely used weight‑loss drugs such as Ozempic, Wegovy, Zepbound and Mounjaro. Their goal: single or infrequent treatments that could reduce cost, dosing burden and some drawbacks of chronic therapy.

How each approach works

RenBio uses a nonviral plasmid delivered into muscle combined with brief electrical pulses (electroporation). The pulses transiently open tiny pores in cell membranes so circular DNA plasmids can enter the cytoplasm and reach the nucleus, where they are read by the cell’s protein‑making machinery. The plasmids remain episomal (do not integrate into chromosomes) and drive production of a GLP‑1 receptor agonist that is secreted into the circulation.

Fractyl uses an adeno‑associated virus (AAV) vector to deliver GLP‑1 instructions directly to pancreatic beta cells. To limit off‑target expression, Fractyl ties the therapeutic sequence to an insulin promoter so only insulin‑producing cells will express extra GLP‑1 and production rises and falls with insulin demand.

Key animal results

Both companies have reported encouraging preclinical results in rodents and have moved into larger‑animal testing (pigs, monkeys). In mice, RenBio reported roughly 15% weight loss sustained for about a year after a single plasmid dose; Fractyl reported about 20% weight loss in obese mice within three weeks and protection from weight gain in treated lean mice fed a high‑fat diet.

Potential advantages

• Fewer injections (potentially once per year or a one‑time AAV dose) compared with daily or weekly GLP‑1 drugs.
• Self‑regulated expression (Fractyl’s insulin promoter) may reduce the risk of excessive hormone exposure.
• Lower long‑term cost and better adherence if safety and durability are proven.

Safety, ethical and regulatory cautions

Experts warn that promising animal results do not guarantee human safety or efficacy. Viral vectors can trigger immune reactions and, in rare cases, insertional mutagenesis; permanent or long‑lasting genetic changes raise concerns about reversibility if overexpression or unanticipated effects occur. Nonviral methods like plasmids avoid integration but the duration of expression and long‑term safety in humans remain uncertain.

“There is promise, but much more data would be needed to consider human clinical trials, as it likely would be irreversible,” said Dr. Donald Kohn, a gene‑therapy expert at UCLA.

Timeline and next steps

Both companies plan further large‑animal testing; Fractyl has filed U.S. regulatory paperwork and expects human data as early as 2026. RenBio is advancing toward human testing of its plasmid platform for other applications and plans clinical work in the coming years, pending regulatory review and funding.

Context: Why it matters

GLP‑1 drugs have rapidly increased in use for weight loss, roughly doubling among U.S. adults from 5.8% to 12% in under two years according to Gallup, and have been linked with a modest drop in national obesity prevalence. Yet they can be costly and commonly cause side effects (nausea, vomiting, fatigue), and many patients stop therapy within a year. Gene‑based approaches aim to capture therapeutic benefits while addressing durability, cost and adherence—if they can be shown safe and controllable in humans.

Bottom line: Early preclinical data are encouraging, but substantial safety testing, regulatory review and ethical debate lie ahead before single‑shot GLP‑1 gene therapies could become a clinical reality.