ArticleMolecular therapy. Methods & clinical development2020
"Para-retinal" Vector Administration into the Deep Vitreous Enhances Retinal Transgene Expression.
Article in Molecular therapy. Methods & clinical development, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 7 citations in OpenAlex.
- Visual Acuity-Related Outer Retinal Structural Parameters on Swept Source Optical Coherence Tomography and Angiography in XLRS Patients and Carriers.Translational vision science & technology · 2023Article
- Outer retinal transduction by AAV2-7m8 following intravitreal injection in a sheep model of CNGA3 achromatopsia.Gene therapy · 2022Article
- Pre-retinal delivery of recombinant adeno-associated virus vector significantly improves retinal transduction efficiency.Molecular therapy. Methods & clinical development · 2021Article
- Delivering AAV to the Central Nervous and Sensory Systems.Trends in pharmacological sciences · 2021Review
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intravitreal administration for human adeno-associated vector (AAV) delivery is easier and less traumatic to ocular tissues than subretinal injection, but it gives limited retinal transduction. AAV vectors are large (about 4,000 kDa) compared with most intraocular drugs, such as ranibizumab (48 kDa), and the large size impedes diffusion to reach the retina from the usual injection site in the anterior/mid-vitreous. Intuitively, a preferred placement for the vector would be deep in the vitreous near the retina, which we term "para-retinal" delivery. We explored the consequences of para-retinal intravitreal delivery in the rabbit eye and in non-human primate (NHP) eye. 1 h after para-retinal administration in the rabbit eye, the vector concentration near the retina remained four times greater than in the anterior vitreous, indicating limited vector diffusion through the gelatinous vitreous matrix. In NHP, para-retinal placement showed greater transduction in the fovea than vector applied in the mid-vitreous. More efficient retinal delivery translates to using lower vector doses, with reduced risk of ocular inflammatory exposure. These results indicate that para-retinal delivery yields more effective vector concentration near the retina, thereby increasing the potential for better retinal transduction in human clinical application.
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