ArticlePloS one2014
Ocular localization and transduction by adenoviral vectors are serotype-dependent and can be modified by inclusion of RGD fiber modifications.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Seeing the Future: A Review of Ocular Therapy.Bioengineering (Basel, Switzerland) · 2024Review
- Delivery strategies for CRISPR/Cas genome editing tool for retinal dystrophies: challenges and opportunities.Asian journal of pharmaceutical sciences · 2022Review
- Viral-Vector-Delivered Anti-Angiogenic Therapies to the Eye.Pharmaceutics · 2021Review
- Recombinant adenovirus causes prolonged mobilization of macrophages in the anterior chambers of mice.Molecular vision · 2021Article
- Human Vascular Endothelial Growth Factor AGenes · 2018Article
- Gene therapy and genome surgery in the retina.The Journal of clinical investigation · 2018Review
- BMP and Activin Membrane Bound Inhibitor Regulates the Extracellular Matrix in the Trabecular Meshwork.Investigative ophthalmology & visual science · 2018Article
- CRISPR-Cas9-based treatment of myocilin-associated glaucoma.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Gene transfer to the outflow tract.Experimental eye research · 2017Review
- Elevation of intraocular pressure in rodents using viral vectors targeting the trabecular meshwork.Experimental eye research · 2015Review
- Gene Delivery by Subconjunctival Injection of Adenovirus in Rats: A Study of Local Distribution, Transgene Duration and Safety.PloS one · 2015Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo evaluate localization and transgene expression from adenoviral vector of serotypes 5, 35, and 28, ± an RGD motif in the fiber following intravitreal or subretinal administration.
methodsOcular transduction by adenoviral vector serotypes ± RGD was studied in the eyes of mice receiving an intravitreous or subretinal injection. Each serotype expressed a CMV-GFP expression cassette and histological sections of eyes were examined. Transgene expression levels were examined using luciferase (Luc) regulated by the CMV promoter.
resultsGFP localization studies revealed that serotypes 5 and 28 given intravitreously transduced corneal endothelial, trabecular, and iris cells. Intravitreous delivery of the unmodified Ad35 serotype transduced only trabecular meshwork cells, but, the modification of the RGD motif into the fiber of the Ad35 viral vector base expanded transduction to corneal endothelial and iris cells. Incorporation of the RGD motif into the fiber knob with deletion of RGD from the penton base did not affect the transduction ability of the Ad5 vector base. Subretinal studies showed that RGD in the Ad5 knob shifted transduction from RPE cells to photoreceptor cells. Using a CMV-Luc expression cassette, intravitreous delivery of all the tested vectors, such as Ad5-, Ad35- and Ad28- resulted in an initial rapid induction of luciferase activity that thereafter declined. Subretinal administration of vectors showed a marked difference in transgene activity. Ad35-Luc gene expression peaked at 7 days and remained elevated for 6 months. Ad28-Luc expression was high after 1 day and remained sustained for one month.
conclusionsDifferent adenoviral vector serotypes ± modifications transduce different cells within the eye. Transgene expression can be brief or extended and is serotype and delivery route dependent. Thus, adenoviral vectors provide a versatile platform for the delivery of therapeutic agents for ocular diseases.
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