The first-ever clinical trial of an adeno-associated virus (AAV) gene therapy for type 1 diabetes (T1D) is set to begin this year.

The PROGRESS study will enroll adults with T1D to receive a one-time intramuscular injection of KRIYA-839 and follow them for 1 year for both safety and efficacy endpoints. The product is designed to promote endogenous expression of glucokinase (GCK) and insulin in the quadriceps muscles, announced Jeremy Pettus, MD, an endocrinologist and associate professor of medicine at the University of California, San Diego, at the 19th International Conference on Advanced Technologies and Treatments for Diabetes (ATTD) 2026.

“In the type 1 community, we’re used to [hearing] this will happen in 10 to 15 years and maybe will come one day. It’s very exciting to stand here and say that this is actually something that’s in the works and happening now,” said Pettus.

Proven Technology

The therapy involves using the nonpathologic AAV vector to deliver two genes, for GCK and insulin, into muscle. These genes then remain in the nuclei of the cells to produce genetic material for the life of the patient.

“It doesn’t integrate with the host genome. It’s not changing the chromosomes,” said Pettus. “This isn’t gene editing or changing genetic makeup.”

Currently approved gene therapy products are mostly for more rare, monogenic diseases. “This is a proven technology,” said Pettus. And “now the manufacturing has improved such that we can move away from the [rare] cases to more common diseases like diabetes.”

Preclinical data demonstrated efficacy and safety of both gene products in normalizing blood glucose levels in mouse and dog models of T1D without immune suppression for up to 4 years, he reported.

Advantages of AAV gene therapy include durable clinical benefit, single administration, no need for chronic immunosuppression, and broad patient eligibility. Unlike current transplants of either cadaver or stem-cell derived islets that require immune suppression and are therefore limited to those with severe hypoglycemia or recurrent diabetic ketoacidosis, this therapy “could potentially be for the masses” with T1D, the researcher said.

In Kriya’s approach, the two genes within the AAV are delivered into the thigh muscle, where the cells aren’t actively dividing. The muscle then secretes insulin, which activates glucose transporter type 4 to bring glucose into the cells, its normal action. For its part, GCK is activated at higher glucose levels to move glucose out of the bloodstream, while remaining inactive when blood glucose levels are low. “So it has a glucose sensing kind of quality to it,” Pettus noted.

Treatment administration would require just a short course of “immune modulation” around the response to the virus capsid. “We’re very careful to use the word ‘modulation,’ not suppression…the idea is to dampen the immune system slightly around the time of injection to help facilitate the uptake of genetic material into the cell,” he explained.

Delivery would likely require several intramuscular injections, likely in both legs, over about 30-60 minutes during one outpatient clinic visit. After that, “it takes 2-3 months to get to a kind of steady state, and then, if all goes well, this could last for the entire life of the patient,” Pettus said.

Kriya’s planned 52-week phase 1 dose escalation study, set to begin this year, will enroll patients with T1D who have A1c levels above 7% while using automated insulin delivery systems. That requirement is for safety, to ensure that insulin dosing can be precisely quantified and de-escalated as needed. But if successful, people who use multiple daily injections would also be eligible, Pettus said.

Potential for a Functional Cure?

Asked to comment, ATTD meeting co-chair Tadej Battelino, MD, head of the Department of Endocrinology at UCH-UMC Ljubljana, Ljubljana, Slovenia, told Medscape Medical News that he wouldn’t use the word “cure” just yet. “I tend to be cautious, so I really can’t give promises….Does this have a potential? Very much so.”

Battelino, who is also chair and professor of pediatrics at the University of Ljubljana, added that even if it’s not a complete “cure,” if it was able to achieve more than 70% of “time in tight range,” ie, 70-140 mg/dL, possibly in combination with technology, then “I’m not saying it’s a cure, but a functional cure, for sure.”

Pettus reported serving as an advisor to Sanofi, Novo Nordisk, and Kriya and on the speakers bureau for Sanofi. Battelino reported receiving research grants (paid to his institution) from Abbott, Medtronic, Novo Nordisk, Sanofi, Novartis, Sandoz, and Zealand Pharma.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR’s Shots blog, and diaTribe. She is on X (formerly Twitter) @MiriamETucker and BlueSky @miriametucker.bsky.social.