Adeno-Associated Virus (AAV)-Mediated Gene Therapy for Leber Hereditary Optic Neuropathy
Leber hereditary optic neuropathy (LHON) is the first clinically characterized maternally inherited mitochondrial disorder. Up to now, more than 30 pathogenic point mutations in mitochondrial DNA (mtDNA) coding for the respiratory chain subunits of complex I genes, which are highly susceptible to disrupted ATP production and oxidative stress, have been identified to cause LHON. The fundamental cell type affected in LHON is the retinal ganglion cells. Many researches facilitated the progress of animal models in vivo and cell culture in vitro that have been used to determine the effects of the genetic mutations upon the clinical phenotype and to explore potential novel therapies. More recently, clinical studies applying gene therapy have shown promising results in treating LHON. This article reviewed the efficacy and safety of recombinant adeno-associated virus 2 carrying ND4 (rAAV2-ND4) in clinical trials and its allotopic expression in the LHON patients with the G11778A mutation, which accounts for the majority of this vision-threatening disorder.
KeywordsLeber hereditary optic neuropathy Allotopic expression AAV2-ND4 Gene therapy Retinal ganglion cell
This study is supported by the National Natural Science Foundation of China grants (81470621, 81770949), National Key Clinical Specialties Construction Program of China, Henan Science and Technology Bureau (182102310145), Henan Provincial Clinical Research Center, and Henan Key Laboratory of Ophthalmology and Visual Science. The authors alone are responsible for the content and writing of the paper.
Compliance with Ethical Requirements
The authors have no conflict of interest to declare.
- 22.Bonnet C, Kaltimbacher V, Ellouze S, Augustin S, Bénit P, Forster V, Rustin P, Sahel J-A, Corral-Debrinski M. Allotopic mRNA localization to the mitochondrial surface rescues respiratory chain defects in fibroblasts harboring mitochondrial DNA mutations affecting complex I or v subunits. Rejuvenation Res. 2007;10(2):127–44.CrossRefGoogle Scholar