Gene therapy for mitochondrial eye diseases

This study aims to demonstrate a proof-of-concept for the use of gene editing to treat blinding eye diseases linked to heteroplasmic mitochondrial DNA (mtDNA) mutations, which are currently untreatable. This proposal builds upon recent breakthroughs from the Minczuk laboratory utilizing mitochondrially targeted zinc-finger nucleases (mtZFNs) to reduce pathogenic mtDNA levels and restore biochemical and molecular phenotypes in the heart of a mouse model carrying a heteroplasmic tRNA mutation. Here we aim to determine whether mtZFNs delivered intravitreally can reduce mutant mtDNA levels and revert molecular and functional phenotypes in the retina in the disease mouse model. This study will provide crucial evidence about the clinical potential of mtZFNs to treat mitochondrial eye diseases. Moreover, it would further validate the use of these gene editing tools to correct other mitochondrial phenotypes caused by heteroplasmic mtDNA mutations.