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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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"Para-retinal" Vector Administration into the Deep Vitreous Enhances Retinal Transgene Expression
Yong Zeng1, Ryan Boyd2, Joshua Bartoe2
1National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Molecular Therapy. Methods & Clinical Development
|July 23, 2020
Summary
Para-retinal intravitreal delivery of adeno-associated vectors (AAV) enhances retinal transduction. This method improves vector concentration near the retina, potentially reducing required doses and ocular inflammation.
Area of Science:
- Ophthalmology
- Gene Therapy
- Biomedical Engineering
Background:
- Intravitreal adeno-associated vector (AAV) delivery offers advantages over subretinal injection but faces challenges in achieving sufficient retinal transduction due to vector size.
- Large AAV vectors (approx. 4,000 kDa) diffuse poorly through the vitreous matrix from anterior/mid-vitreous injection sites, limiting retinal targeting compared to smaller drugs like ranibizumab (48 kDa).
Purpose of the Study:
- To investigate the efficacy of a novel "para-retinal" intravitreal delivery approach for enhancing AAV vector concentration and transduction in the retina.
- To compare the distribution and transduction efficiency of para-retinal AAV delivery versus traditional mid-vitreous delivery in ocular models.
Main Methods:
- Para-retinal intravitreal injections of AAV vectors were administered in rabbit and non-human primate (NHP) eyes.
- Vector concentration near the retina was measured at 1 hour post-injection in rabbits.
- Retinal transduction, particularly in the fovea, was assessed in NHPs following para-retinal and mid-vitreous delivery.
Main Results:
- In rabbit eyes, para-retinal delivery maintained a fourfold higher vector concentration near the retina compared to the anterior vitreous 1 hour post-injection.
- Non-human primates receiving para-retinal AAV delivery demonstrated superior foveal transduction compared to those receiving mid-vitreous injections.
- These findings suggest limited diffusion of AAV vectors through the vitreous gel.
Conclusions:
- Para-retinal intravitreal delivery represents a promising strategy for improving AAV vector concentration and retinal transduction efficiency.
- This approach holds potential for reducing AAV vector doses and mitigating ocular inflammatory responses in future human clinical applications for retinal gene therapy.
