Aug 05, 2026 —
Kriya Therapeutics announced the publication of preclinical data showing that a single intramuscular administration of an AAV vector expressing native FGF21 extended both health span and lifespan in naturally aged mice.
The study, titled “AAV-mediated FGF21 gene therapy promotes health span extension by whole-body tissue-specific adaptations,” was led by Professor Fátima Bosch at the Center for Animal Biotechnology and Gene Therapy at the Universitat Autònoma de Barcelona. The findings were published in Molecular Therapy, the founding journal of the American Society of Gene & Cell Therapy.
FGF21 is a metabolic hormone involved in regulating energy balance across multiple tissues, including muscle, liver, fat, and brain. Kriya said the findings support the systemic biology underlying its native FGF21 gene therapy candidate, KRIYA-497, which is being developed for steatotic liver disease and other conditions where FGF21 biology may be relevant.
In the study, a single intramuscular dose of AAV1-FGF21 in aged mice increased life expectancy by more than 20%, extending median lifespan by nearly six months.
Treated animals also showed broad metabolic benefits, including normalized body weight and adiposity, improved insulin sensitivity and glucose control, and increased energy expenditure.
The therapy produced sustained benefits across multiple organ systems. Liver, kidney, and heart function were preserved, while age-related kidney damage, fibrosis, and amyloidosis were prevented.
Functional outcomes were also improved. Muscle strength, endurance, and memory were maintained at levels comparable to much younger animals.
Transcriptomic analyses linked these benefits to tissue-specific adaptations, including enhanced mitochondrial function, restored protein synthesis, improved hepatic detoxification, and reduced inflammation and fibrosis.
The findings build on prior preclinical work showing that AAV-FGF21 gene therapy can counteract established metabolic dysfunction-associated steatohepatitis, or MASH, type 2 diabetes, and obesity in disease models.
Kriya’s clinical candidate KRIYA-497 is a one-time gene therapy designed to express human native FGF21. The therapy is currently being evaluated in a clinical trial for patients with MASH and remains investigational.
The publication adds to growing interest in AAV-based metabolic gene therapy, particularly approaches designed to deliver durable systemic effects through long-term expression of therapeutic proteins. For KRIYA-497, the next key questions will include clinical safety, dose selection, durability of FGF21 expression, and whether the broad metabolic effects observed in animals translate to patients with steatotic liver disease.
