MILAN, Italy, July 8, 2026
Genespire, in collaboration with researchers at the San Raffaele Telethon Institute for Gene Therapy (SR-TIGET), announced the publication of promising preclinical data demonstrating the long-term therapeutic potential of its liver-directed immune-shielded lentiviral (ISLV) gene therapy platform for the treatment of methylmalonic acidemia (MMA). Published in the Journal of Hepatology, the study showed that a single systemic administration of a lentiviral vector carrying the MMUT gene produced durable therapeutic benefits in validated mouse models of MMA, with treatment effects lasting throughout the animals’ average lifespan. Because therapy was administered during early life, the findings also demonstrated sustained gene expression during postnatal liver growth and maturation, supporting the potential of the platform to provide long-lasting disease correction following a single treatment. Methylmalonic acidemia is a rare inherited metabolic disorder caused by deficiency of the methylmalonyl-CoA mutase (MMUT) enzyme, resulting in toxic metabolite accumulation, metabolic crises, neurological impairment, growth failure, and progressive multi-organ damage.
Optimized MMUT Gene Improves Therapeutic Performance
The investigators also evaluated an optimized MMUT transgene, which further enhanced therapeutic efficacy in the same preclinical disease model. The optimized construct produced dose-dependent improvements in key metabolomic biomarkers while achieving gene transfer efficiency exceeding 80% of liver cells, representing a significant milestone for systemic liver-directed gene therapy. Researchers further observed evidence that genetically corrected liver cells gradually replaced diseased cells over time, suggesting that therapeutic benefit may continue to increase after treatment, even when lower initial doses are administered. This progressive replacement of dysfunctional hepatocytes provides additional support for the durability and regenerative potential of Genespire’s immune-shielded lentiviral vector technology, which is designed to deliver long-term gene expression while minimizing immune-related limitations commonly associated with other gene therapy platforms.
GENE202 Advances Toward Clinical Development
According to Genespire Chief Executive Officer Lucia Faccio, the latest findings strengthen confidence that the company’s immune-shielded lentiviral vector (ISLV) platform can deliver durable correction of inherited metabolic diseases affecting both the liver and multiple organ systems. She noted that the encouraging results support continued advancement of GENE202, the company’s lead investigational gene therapy for methylmalonic acidemia, toward human clinical studies. The therapy is designed as a single-administration treatment capable of enabling long-term production of the therapeutic protein directly within the patient’s liver following intravenous administration. Dr. Alessio Cantore, Group Leader at SR-TIGET and Associate Professor at Vita-Salute San Raffaele University, added that the current study, together with previous research from the institute, provides a comprehensive preclinical evidence package supporting the initiation of clinical testing in pediatric patients affected by MMA.
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Gene Therapy Platform Targets Rare Pediatric Metabolic Diseases
Genespire is developing a pipeline of off-the-shelf immune-shielded lentiviral vector-based gene therapies focused on rare pediatric genetic diseases with significant unmet medical need. Originating as a spin-out of SR-TIGET, one of the world’s leading gene therapy research institutions, the company has designed its proprietary ISLV platform to enable intravenous delivery while supporting lifelong therapeutic protein production directly from the liver. The positive Journal of Hepatology publication reinforces the scientific foundation of GENE202 and highlights the broader potential of immune-shielded lentiviral gene therapy for inherited metabolic disorders. As the company advances its lead program toward clinical evaluation, the durable efficacy, high liver transduction efficiency, and favorable regenerative findings position GENE202 as a promising investigational therapy for patients living with methylmalonic acidemia, a disease for which effective long-term treatment options remain extremely limited.
Source:Genespire press release
