Liver-directed lentiviral gene therapy confers durable hepatic and systemic amelioration of methylmalonic acidemia in mice.

Liver-directed lentiviral gene therapy achieves long-lasting metabolic correction in MMA mice, with over 80% hepatocyte transduction and therapeutic effects lasting more than a year.

• Why it matters: Methylmalonic acidemia is a severe inherited disorder with limited treatment options, and effective therapies are needed to address its systemic metabolic impact, especially in pediatric patients.
• What they did: The study used systemic delivery of an MMUT-expressing lentiviral vector in MMA mice and patient fibroblasts, demonstrating dose-dependent improvements in metabolic biomarkers, clinical phenotype, and enzyme expression.
• The result: This gene therapy normalized liver and systemic metabolism, improved disease symptoms, and showed a favorable safety profile, supporting progression to clinical trials for MMA and similar metabolic diseases.