Gene Therapy Intervention in Neovascular Eye Disease: A Recent Update
Open accessAbstract
Aberrant growth of blood vessels (neovascularization) is a key feature of severe eye diseases that can cause legal blindness, including neovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR). The development of anti-vascular endothelial growth factor (VEGF) agents has revolutionized the treatment of ocular neovascularization. Novel proangiogenic targets, such as angiopoietin and platelet-derived growth factor (PDGF), are under development for patients who respond poorly to anti-VEGF therapy and to reduce adverse effects from long-term VEGF inhibition. A rapidly advancing area is gene therapy, which may provide significant therapeutic benefits. Viral vector-mediated transgene delivery provides the potential for continuous production of antiangiogenic proteins, which would avoid the need for repeated anti-VEGF injections. Gene silencing with RNA interference to target ocular angiogenesis has been investigated in clinical trials. Proof-of-concept gene therapy studies using gene-editing tools such as CRISPR-Cas have already been shown to be effective in suppressing neovascularization in animal models, highlighting the therapeutic potential of the system for treatment of aberrant ocular angiogenesis. This review provides updates on the development of anti-VEGF agents and novel antiangiogenic targets. We also summarize current gene therapy strategies already in clinical trials and those with the latest approaches utilizing CRISPR-Cas gene editing against aberrant ocular neovascularization.
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Intravitreal anti-VEGF drugs are the approved front-line treatment for DR and nAMD.
“Intravitreal administration of anti-VEGF drugs is the approved front-line treatment modality for these patients (17).”
From Characterization of RNA editing and gene therapy with a compact CRISPR-Cas13 in the retina (2024) · cites this paper as [17]
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- Authors
- Lin, F.-L., Wang, P.-Y., Chuang, Y.-F., Wang, J.-H., Wong, V. H. Y., Bui, B. V., & Liu, G.-S.
- Affiliations
- University of Tasmania (AU)
- Chinese Academy of Sciences (CN)
- The Royal Victorian Eye & Ear Hospital (AU)
- The University of Melbourne (AU)
- Corresponding author
- Wang, Peng-Yuan
- Liu, Guei-Sheung
- Venue
- Molecular Therapy
- Publisher
- Elsevier BV
- Published
- 2020-10
- Volume
- 28
- Issue
- 10
- Pages
- 2120-2138
- ISSN
- 1525-0016 (ISSN-L)
- PMC
- PMC7544979
- OpenAlex
- W3038555270
- Cited by
- 74
- References
- 235
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 15 · 2023: 13 · 2022: 14 · 2021: 10 · 2020: 2
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Molecular Therapy (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UTAS Research Repository (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-nd)
- Swinburne figshare (Swinburne University of Technology) (submittedVersion)
- Funders
- National Health and Medical Research Council (GNT1185600)
- Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences (ZDSYS20190902093409851)
- State Government of Victoria
- Ophthalmic Research Institute of Australia
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- gene therapy, neovascularization, ocular angiogenesis, neovascular age-related macular degeneration, diabetic retinopathy, anti-VEGF therapy, vascular endothelial growth factor, angiopoietins, platelet-derived growth factor, RNA interference, CRISPR gene editing
- MeSH terms
- Gene Editing, Animals, Clinical Trials as Topic, Disease Susceptibility, Eye Diseases, Humans, Neovascularization, Pathologic, Platelet-Derived Growth Factor, Genetic Therapy, Treatment Outcome, Disease Management, Vascular Endothelial Growth Factor A, CRISPR-Cas Systems
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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