Frontiers in Genetics (Jan 2022)
Gene-Based Therapeutics for Inherited Retinal Diseases
- Beau J. Fenner,
- Beau J. Fenner,
- Beau J. Fenner,
- Tien-En Tan,
- Tien-En Tan,
- Tien-En Tan,
- Amutha Veluchamy Barathi,
- Sai Bo Bo Tun,
- Sia Wey Yeo,
- Andrew S. H. Tsai,
- Andrew S. H. Tsai,
- Andrew S. H. Tsai,
- Shu Yen Lee,
- Shu Yen Lee,
- Shu Yen Lee,
- Chui Ming Gemmy Cheung,
- Chui Ming Gemmy Cheung,
- Chui Ming Gemmy Cheung,
- Choi Mun Chan,
- Choi Mun Chan,
- Choi Mun Chan,
- Jodhbir S. Mehta,
- Jodhbir S. Mehta,
- Jodhbir S. Mehta,
- Jodhbir S. Mehta,
- Jodhbir S. Mehta,
- Kelvin Y. C. Teo,
- Kelvin Y. C. Teo,
- Kelvin Y. C. Teo
Affiliations
- Beau J. Fenner
- Singapore National Eye Centre, Singapore, Singapore
- Beau J. Fenner
- Singapore Eye Research Institute, Singapore, Singapore
- Beau J. Fenner
- Duke-NUS Graduate Medical School, Ophthalmology and Visual Sciences Academic Clinical Programme, Singapore, Singapore
- Tien-En Tan
- Singapore National Eye Centre, Singapore, Singapore
- Tien-En Tan
- Singapore Eye Research Institute, Singapore, Singapore
- Tien-En Tan
- Duke-NUS Graduate Medical School, Ophthalmology and Visual Sciences Academic Clinical Programme, Singapore, Singapore
- Amutha Veluchamy Barathi
- Singapore Eye Research Institute, Singapore, Singapore
- Sai Bo Bo Tun
- Singapore Eye Research Institute, Singapore, Singapore
- Sia Wey Yeo
- Singapore Eye Research Institute, Singapore, Singapore
- Andrew S. H. Tsai
- Singapore National Eye Centre, Singapore, Singapore
- Andrew S. H. Tsai
- Singapore Eye Research Institute, Singapore, Singapore
- Andrew S. H. Tsai
- Duke-NUS Graduate Medical School, Ophthalmology and Visual Sciences Academic Clinical Programme, Singapore, Singapore
- Shu Yen Lee
- Singapore National Eye Centre, Singapore, Singapore
- Shu Yen Lee
- Singapore Eye Research Institute, Singapore, Singapore
- Shu Yen Lee
- Duke-NUS Graduate Medical School, Ophthalmology and Visual Sciences Academic Clinical Programme, Singapore, Singapore
- Chui Ming Gemmy Cheung
- Singapore National Eye Centre, Singapore, Singapore
- Chui Ming Gemmy Cheung
- Singapore Eye Research Institute, Singapore, Singapore
- Chui Ming Gemmy Cheung
- Duke-NUS Graduate Medical School, Ophthalmology and Visual Sciences Academic Clinical Programme, Singapore, Singapore
- Choi Mun Chan
- Singapore National Eye Centre, Singapore, Singapore
- Choi Mun Chan
- Singapore Eye Research Institute, Singapore, Singapore
- Choi Mun Chan
- Duke-NUS Graduate Medical School, Ophthalmology and Visual Sciences Academic Clinical Programme, Singapore, Singapore
- Jodhbir S. Mehta
- Singapore National Eye Centre, Singapore, Singapore
- Jodhbir S. Mehta
- Singapore Eye Research Institute, Singapore, Singapore
- Jodhbir S. Mehta
- Duke-NUS Graduate Medical School, Ophthalmology and Visual Sciences Academic Clinical Programme, Singapore, Singapore
- Jodhbir S. Mehta
- School of Material Science and Engineering, Nanyang Technological University, Singapore, Singapore
- Jodhbir S. Mehta
- Yong Loo Lin School of Medicine, Department of Ophthalmology, National University of Singapore, Singapore, Singapore
- Kelvin Y. C. Teo
- Singapore National Eye Centre, Singapore, Singapore
- Kelvin Y. C. Teo
- Singapore Eye Research Institute, Singapore, Singapore
- Kelvin Y. C. Teo
- Duke-NUS Graduate Medical School, Ophthalmology and Visual Sciences Academic Clinical Programme, Singapore, Singapore
- DOI
- https://doi.org/10.3389/fgene.2021.794805
- Journal volume & issue
-
Vol. 12
Abstract
Inherited retinal diseases (IRDs) are a heterogenous group of orphan eye diseases that typically result from monogenic mutations and are considered attractive targets for gene-based therapeutics. Following the approval of an IRD gene replacement therapy for Leber’s congenital amaurosis due to RPE65 mutations, there has been an intensive international research effort to identify the optimal gene therapy approaches for a range of IRDs and many are now undergoing clinical trials. In this review we explore therapeutic challenges posed by IRDs and review current and future approaches that may be applicable to different subsets of IRD mutations. Emphasis is placed on five distinct approaches to gene-based therapy that have potential to treat the full spectrum of IRDs: 1) gene replacement using adeno-associated virus (AAV) and nonviral delivery vectors, 2) genome editing via the CRISPR/Cas9 system, 3) RNA editing by endogenous and exogenous ADAR, 4) mRNA targeting with antisense oligonucleotides for gene knockdown and splicing modification, and 5) optogenetic approaches that aim to replace the function of native retinal photoreceptors by engineering other retinal cell types to become capable of phototransduction.
Keywords
- inherited retinal diseases (IRDs)
- gene tharapy
- adeno-associated virus
- RNA editing
- CRISPR
- optogenetic