Gene therapy in hereditary retinal dystrophy

Jia-Ying Chien; Shun-Ping Huang

doi:10.4103/tcmj.tcmj_78_22

Gene therapy in hereditary retinal dystrophy

Tzu Chi Med J. 2022 Aug 23;34(4):367-372. doi: 10.4103/tcmj.tcmj_78_22. eCollection 2022 Oct-Dec.

Authors

Jia-Ying Chien¹, Shun-Ping Huang^{1

2

3}

Affiliations

¹ Institute of Medical Science, Tzu Chi University, Hualien, Taiwan.
² Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan.
³ Department of Ophthalmology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan.

Abstract

Hereditary retinal dystrophies (HRDs), such as retinitis pigmentosa, Leber's congenital amaurosis (LCA), Usher syndrome, and retinoschisis, are a group of genetic retinal disorders exhibiting both genetic and phenotypic heterogeneity. Symptoms include progressive retinal degeneration and constricted visual field. Some patients will be legal or completely blind. Advanced sequencing technologies improve the genetic diagnosis of HRD and lead to a new era of research into gene-targeted therapies. Following the first Food and Drug Administration approval of gene augmentation therapy for LCA caused by RPE65 mutations, multiple clinical trials are currently underway applying different techniques. In this review, we provide an overview of gene therapy for HRD and emphasize four distinct approaches to gene-targeted therapy that have the potential to slow or even reverse retinal degeneration: (1) viral vector-based and nonviral gene delivery, (2) RNA-based antisense oligonucleotide, (3) genome editing by the Clustered Regularly Interspaced Short Palindromic Repeat/cas9 system, and (4) optogenetics gene therapy.

Keywords: Antisense oligonucleotides; Clustered Regularly Interspaced Short Palindromic Repeat/cas system; Gene therapy; Optogenetics; Retinal dystrophy.

Publication types

Review