Mitochondria-targeted gene delivery using fluorinated lipid nanoparticles to alleviate Leber's hereditary optic neuropathy.

ABSTRACT: Mutations in mitochondrial DNA (mtDNA) lead to various mitochondrial diseases for which no cure is currently available. Despite the promising potential of mtDNA correction to treat these disorders, the double mitochondrial membranes have proven to be a tough barrier to overcome. Here, we develop fluorinated lipid nanoparticles with a mitochondrial targeting sequence (F-M-LNP) to overcome the mitochondrial barrier by virtue of their high affinity for mitochondrial membranes, thereby effectively introducing gene into mitochondria. Through the rational design of ionizable lipid structures, we synthesize 16 lipid nanoparticles (LNPs) with varying degrees of fluorination and investigate the key structural features required for efficient mitochondria-targeted gene delivery. As fluorinated ioniza

SUBMITTER: Wang Y 

PROVIDER: S-EPMC12678772 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature