April 22, 2026 —
A first-in-human clinical trial of an Adeno-associated virus (AAV) gene therapy for type 1 diabetes (T1D) is set to begin this year, led by Kriya Therapeutics. The investigational therapy, KRIYA-839, aims to enable long-term insulin production directly within muscle tissue—potentially transforming how this chronic disease is treated.
The upcoming PROGRESS study will evaluate the safety and efficacy of a one-time intramuscular injection in adult T1D patients over a 52-week period. The program was highlighted at the ATTD 2026 by Jeremy Pettus of University of California San Diego, who emphasized that this approach represents a meaningful shift from traditional insulin replacement toward a potentially durable therapeutic solution.
KRIYA-839 leverages AAV to deliver two genes—insulin and glucokinase (GCK)—into skeletal muscle cells. Unlike gene editing technologies, this platform does not integrate into the host genome. Instead, the delivered genes persist episomally in the nucleus, enabling sustained expression without altering the patient’s DNA.
The biology behind the approach is particularly compelling. Muscle cells act as a “biofactory,” producing insulin in response to circulating glucose levels. The addition of GCK introduces a built-in glucose-sensing mechanism, activating only when blood sugar is elevated and helping regulate glucose homeostasis more physiologically.
Preclinical studies in mouse and canine models have demonstrated durable glucose control for up to four years without the need for chronic immunosuppression. This differentiates the therapy from islet transplantation strategies, which require lifelong immune suppression and are limited to a subset of patients with severe disease.
Treatment administration is expected to involve multiple intramuscular injections delivered during a single outpatient visit, supported by short-term immune modulation to facilitate vector uptake. Clinical effects are anticipated to stabilize within a few months, with the potential for long-term durability.
While experts caution against labeling the approach a “cure” at this stage, the possibility of achieving sustained glycemic control—potentially reaching clinically meaningful thresholds such as >70% time in range—positions this therapy as a candidate for a functional cure.
If successful, Kriya’s program could represent a major milestone for gene therapy, demonstrating that AAV-based platforms can extend beyond rare diseases into large, chronic indications like diabetes, fundamentally reshaping treatment paradigms for millions of patients.
