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Adeno-Associated Virus (AAV)-Mediated Gene Therapy for Leber Hereditary Optic Neuropathy

  • Kunpeng Xie
  • Shuai Ming
  • Mingzhu Yang
  • Xuemin Jin
  • Bo Lei
Chapter
Part of the Essentials in Ophthalmology book series (ESSENTIALS)

Abstract

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.

Keywords

Leber hereditary optic neuropathy Allotopic expression AAV2-ND4 Gene therapy Retinal ganglion cell 

Notes

Acknowledgments

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.

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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Kunpeng Xie
    • 1
  • Shuai Ming
    • 1
  • Mingzhu Yang
    • 1
  • Xuemin Jin
    • 1
  • Bo Lei
    • 1
  1. 1.Henan Eye Institute, Henan Eye Hospital, Henan Provincial People’s HospitalZhengzhouChina

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