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Limbal Approach-Subretinal Injection of Viral Vectors for Gene Therapy in Mice Retinal Pigment Epithelium
Published on: August 7, 2015
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Suprachoroidal gene transfer with nonviral nanoparticles
Jikui Shen1, Jayoung Kim2,3, Stephany Y Tzeng2,3
1Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Science Advances
|September 16, 2020
Summary
Suprachoroidal injection of nanoparticles offers a promising, repeatable gene therapy alternative for eye diseases, overcoming viral vector limitations like immune response and low cargo capacity.
Area of Science:
- Ophthalmology
- Gene Therapy
- Nanotechnology
Background:
- Subretinal viral vector injections are effective but limited by immune responses, low cargo capacity, and administration risks.
- Repeated subretinal injections are often precluded due to induced immune responses and potential tissue damage.
Purpose of the Study:
- To evaluate suprachoroidal injection of biodegradable nanoparticles (NPs) as a nonviral gene transfer method for ocular applications.
- To assess the expression levels, duration, and therapeutic potential of NP-mediated gene delivery in a rat model.
Main Methods:
- Biodegradable NPs containing reporter or therapeutic plasmids were injected suprachoroidally in rats.
- Reporter gene expression in photoreceptors and RPE was monitored over 8 months.
- VEGF-induced neovascularization and therapeutic protein effects were evaluated.
Main Results:
- Suprachoroidal NP injection achieved widespread reporter expression in rat eyes, lasting over 8 months.
- Multiple injections significantly enhanced expression levels.
- VEGF plasmid delivery induced subretinal neovascularization and fibrosis, modeling age-related macular degeneration.
- VEGF-binding protein delivery suppressed vascular leakage and neovascularization, demonstrating therapeutic efficacy.
Conclusions:
- Nonviral NP suprachoroidal gene transfer is a viable, noninvasive alternative to subretinal viral vector delivery.
- This method offers potential for repeatable ocular gene therapy with sustained expression.
- Suprachoroidal NP delivery provides a novel model for neovascular eye diseases and therapeutic development.
