Preclinical Assessment of Mitochondrial-Targeted ND4 Gene Therapy for Leber Hereditary Optic Neuropathy

Intravitreal delivery of MTSAAV/hND4 in rodents resulted in favorable biodistribution, with vector DNA largely confined to the injected eye and minimal systemic exposure. No vector-related adverse effects were observed based on functional, anatomic, and histopathological assessments, supporting the ocular safety of this gene therapy strategy. These findings provide preclinical evidence supporting the advancement of MTSAAV-mediated ND4 gene therapy toward clinical trials for LHON.