RNA-targeting strategies as a platform for ocular gene therapy
Open accessAbstract
Genetic medicine is offering hope as new therapies are emerging for many previously untreatable diseases. The eye is at the forefront of these advances, as exemplified by the approval of Luxturna® by the United States Food and Drug Administration (US FDA) in 2017 for the treatment of one form of Leber Congenital Amaurosis (LCA), an inherited blindness. Luxturna® was also the first in vivo human gene therapy to gain US FDA approval. Numerous gene therapy clinical trials are ongoing for other eye diseases, and novel delivery systems, discovery of new drug targets and emerging technologies are currently driving the field forward. Targeting RNA, in particular, is an attractive therapeutic strategy for genetic disease that may have safety advantages over alternative approaches by avoiding permanent changes in the genome. In this regard, antisense oligonucleotides (ASO) and RNA interference (RNAi) are the currently popular strategies for developing RNA-targeted therapeutics. Enthusiasm has been further fuelled by the emergence of clustered regularly interspersed short palindromic repeats (CRISPR)-CRISPR associated (Cas) systems that allow targeted manipulation of nucleic acids. RNA-targeting CRISPR-Cas systems now provide a novel way to develop RNA-targeted therapeutics and may provide superior efficiency and specificity to existing technologies. In addition, RNA base editing technologies using CRISPR-Cas and other modalities also enable precise alteration of single nucleotides. In…
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CRISPR-Cas13 is exclusively specific for RNA.
“Among CRISPR-Cas proteins, CRISPR-Cas13 is of particular interest for its exclusive specificity for RNA.”
From Characterization of RNA editing and gene therapy with a compact CRISPR-Cas13 in the retina (2024) · cites this paper as [2]
Targeting RNA enables control of gene expression without perturbing the genome and introducing permanent changes.
“Targeting RNA is especially attractive as it enables control of gene expression without perturbing the genome and introducing permanent changes and is therefore an emerging avenue for therapeutic development (2).”
From Characterization of RNA editing and gene therapy with a compact CRISPR-Cas13 in the retina (2024) · cites this paper as [2]
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Characterization of RNA editing and gene therapy with a compact CRISPR-Cas13 in the retina
Kumar, S., Hsiao, Y.-W., Wong, V. H. Y., Aubin, D., Wang, J.-H., Lisowski, L., Rakoczy, E. P., Li, F., Alarcon-Martinez, L., Gonzalez-Cordero, A., et al. (2024) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2408345121 · Cited by 19 · see citing works
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- Authors
- Kumar, S., Fry, L. E., Wang, J.-H., Martin, K. R., Hewitt, A. W., Chen, F. K., & Liu, G.-S.
- Affiliations
- University of Tasmania (AU)
- University of Oxford (GB)
- The Royal Victorian Eye & Ear Hospital (AU)
- The University of Melbourne (AU)
- Lions Eye Institute (AU)
- Corresponding author
- Liu, Guei-Sheung
- ORCID
- Venue
- Progress in Retinal and Eye Research
- Publisher
- Elsevier BV
- Published
- 2023-01
- Volume
- 92
- Pages
- 101110
- ISSN
- 1350-9462 (ISSN-L)
- OpenAlex
- W4285098544
- Cited by
- 51
- References
- 12
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 17 · 2023: 9
- FWCI
- 1.07
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Licence
- Locations
- Progress in Retinal and Eye Research (publishedVersion)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Minerva Access (University of Melbourne) (submittedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Funders
- State Government of Victoria
- National Health and Medical Research Council (1185600)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- ocular gene therapy, RNA-targeting therapeutics, antisense oligonucleotides, RNA interference, CRISPR-Cas, RNA base editing, Leber congenital amaurosis, Luxturna, eye diseases
- MeSH terms
- Gene Editing, Eye Diseases, Humans, RNA, Genetic Therapy, CRISPR-Cas Systems
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