Leber遗传性视神经病变（Leber’s Hereditary Optic Neuropathy, LHON）是由线粒体DNA突变引起的罕见病，也是世界上青壮年致盲的重要因素。目前仅有一种治疗药物艾地苯醌（Idebenone，Ide）可用，但Ide对LHON的治疗以缓解症状，减缓视力损伤为主，无法治本。为克服这一困难，针对LHON的病理特性，本项目提出药物-基因-靶向递送三位一体的治疗策略，构建一种靶向递送治疗基因到线粒体的功能载体Ide-RH-X。该载体可包载治疗基因形成纳米粒，眼内注射后，载体中R基团的穿膜特性与H基团的质子缓冲能力可促进纳米粒的高效摄取与内涵体逃脱，进入细胞质后借助药物Ide与X基团双重靶向，将治疗基因有效带入线粒体基质表达治疗蛋白，同时Ide降低活性氧水平，实现对LHON的标本兼治。这种药物-基因-靶向三位一体的多功能体系为罕见病LHON提供创新性的治疗平台。

Leber's Hereditary Optic Neuropathy (LHON) is a mitochondrial DNA (mtDNA) mutation genetic disorder, which is also one of the world’s most important causal factors of young blindness. However, currently now only one drug (Idebenone, Ide) is available for slowing down vision damage but not cure. To resolve the problem, for LHON case characteristics, this project puts forward trinity treatment strategy combining drug, gene, and targeting therapy, and constructs a kind of mitochondrial targeting functional gene carrier (Ide-RH-X). Therapeutic gene-loaded Ide-RH-X vector formed into nanoparticles, and administered via intraocular injection. The cell-penetrating characteristic of R can improve uptake of nanoparticles, and the proton buffering capacity owning to H is beneficial for the escape of nanoparticles from the endosome. The therapeutic gene of LHON is efficiently transport into mitochondrial matrix due to mitochondrial targeted groups Ide and X. The expressed therapeutic proteins and the reducing oxidation effect of Ide contribute to realize the treatment of LHON. The development of trinity treatment strategy combining drug, gene, and targeting therapy, offers great potential for the treatment of rare diseases like LHON.