Genespire reports preclinical success of liver-directed lentiviral gene therapy for methylmalonic acidemia

Genespire, in partnership with researchers at the San Raffaele Telethon Institute for Gene Therapy (SR‑TIGET), has published preclinical data indicating that its liver‑directed, immune‑shielded lentiviral gene therapy could treat methylmalonic acidemia (MMA). The study demonstrates that the therapeutic vector can deliver functional copies of the MUT gene to hepatocytes while evading host immune responses, a key hurdle in systemic gene therapy for metabolic disorders.

MMA is a severe inherited metabolic disease caused by mutations that impair the conversion of methylmalonyl‑CoA to succinyl‑CoA, leading to toxic metabolite accumulation and life‑threatening complications. The preclinical work shows sustained expression of the corrective gene in animal models, reduction of plasma methylmalonic acid levels, and no detectable off‑target effects or immune activation. The immune‑shielding strategy, which incorporates a cloaking mechanism around the viral capsid, enhances vector persistence and minimizes the need for immunosuppression.

These findings lay the groundwork for future clinical evaluation. If translated successfully to humans, the therapy could offer a durable, one‑time treatment for MMA patients, potentially reducing reliance on lifelong dietary restrictions and regular infusions. The collaboration between Genespire and SR‑TIGET underscores a growing trend toward targeted, immune‑compatible gene therapies for rare metabolic diseases.