A San Raffaele Telethon Institute for Gene Therapy team evaluated liver-directed lentiviral vector gene therapy in a mouse model of methylmalonic acidemia and in patient-derived human fibroblasts. The preclinical work supports the feasibility of a durable hepatic approach for correcting metabolic dysfunction in a rare inherited disorder. For gene therapy developers, the key scrutiny points are vector performance, transgene expression kinetics, and functional correction across relevant biological models. The inclusion of patient-derived fibroblasts helps bridge translation from animal findings to human cell biology. While this is not yet a clinical trial report, the results strengthen the pipeline rationale for moving toward IND-enabling or early clinical studies in a setting where durable biochemical control is the major goal.