ArticleJournal of controlled release : official journal of the Controlled Release Society2013
Persistence of non-viral vector mediated RPE65 expression: case for viability as a gene transfer therapy for RPE-based diseases.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 45 citations in OpenAlex.
- Nanotherapy for Neural Retinal Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Non-viral gene therapy for Leber's congenital amaurosis: progress and possibilities.Nanomedicine (London, England) · 2025Review
- Non-Viral Delivery Systems to Transport Nucleic Acids for Inherited Retinal Disorders.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Effective intravitreal gene delivery to retinal pigment epithelium with hyaluronic acid nanospheres.Molecular therapy. Nucleic acids · 2024Article
- Gene Augmentation of CHM Using Non-Viral Episomal Vectors in Models of Choroideremia.International journal of molecular sciences · 2023Article
- Successful large gene augmentation of USH2A with non-viral episomal vectors.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Directing the Way-Receptor and Chemical Targeting Strategies for Nucleic Acid Delivery.Pharmaceutical research · 2023Review
- Minicircle Delivery to the Neural Retina as a Gene Therapy Approach.International journal of molecular sciences · 2022Review
- Effective gene therapy of Stargardt disease with PEG-ECO/Molecular therapy. Nucleic acids · 2022Article
- Mesoporous Silica-Based Nanoparticles as Non-Viral Gene Delivery Platform for Treating Retinitis Pigmentosa.Journal of clinical medicine · 2022Article
- The Ocular Gene Delivery Landscape.Biomolecules · 2021Review
- Physical and mechanical cues affecting biomaterial-mediated plasmid DNA delivery: insights into non-viral delivery systems.Journal, genetic engineering & biotechnology · 2021Review
- The Landscape of Non-Viral Gene Augmentation Strategies for Inherited Retinal Diseases.International journal of molecular sciences · 2021Review
- Formulation and efficacy of ECO/pRHO-ABCA4-SV40 nanoparticles for nonviral gene therapy of Stargardt disease in a mouse model.Journal of controlled release : official journal of the Controlled Release Society · 2021Article
- Gene Therapy to the Retina and the Cochlea.Frontiers in neuroscience · 2021Review
- Nanotechnology in regenerative ophthalmology.Advanced drug delivery reviews · 2019Review
- Nanoparticles as Delivery Vehicles for the Treatment of Retinal Degenerative Diseases.Advances in experimental medicine and biology · 2018Review
- DNA nanoparticles are safe and nontoxic in non-human primate eyes.International journal of nanomedicine · 2018Article
- Recent perspectives on the delivery of biologics to back of the eye.Expert opinion on drug delivery · 2017Review
- Non-viral therapeutic approaches to ocular diseases: An overview and future directions.Journal of controlled release : official journal of the Controlled Release Society · 2015Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in the retinal pigment epithelium (RPE) gene RPE65 are associated with multiple blinding diseases including Leber's Congenital Amaurosis (LCA). Our goal has been to develop persistent, effective non-viral genetic therapies to treat this condition. Using precisely engineered DNA vectors and high capacity compacted DNA nanoparticles (NP), we previously demonstrated that both plasmid and NP forms of VMD2-hRPE65-S/MAR improved the disease phenotypes in an rpe65(-/-) model of LCA up to 6 months post-injection (PI), however the duration of this treatment efficacy was not established. Here, we test the ability of these vectors to sustain gene expression and phenotypic improvement for the life of the animal. NPs or naked DNA were subretinally injected in rpe65(-/-) mice at postnatal day (P) 16 and evaluated at 15 months PI. Quantitative real-time PCR (qRT-PCR) and immunofluorescence were performed at PI-15 months and demonstrated appreciable expression of transferred RPE65 (levels were 32% of wild-type [WT] for NPs and 44% of WT for naked DNA). No reduction in expression at the message level was observed from PI-6 month data. Spectral electroretinography (ERG) demonstrated significant improvement in cone ERG amplitudes in treated versus uninjected animals. Most importantly, we also observed reduced fundus autofluorescence in the eyes injected with NP and naked DNA compared to uninjected counterparts. Consistent with these observations, biochemical studies showed a reduction in the accumulation of toxic retinyl esters in treated mice, suggesting that the transferred hRPE65 was functional. These critical results indicate that both NP and uncompacted plasmid VMD2-hRPE65-S/MAR can mediate persistent, long-term improvement in an RPE-associated disease phenotype, and suggest that DNA NPs, which are non-toxic and have a large payload capacity, expand the treatment repertoire available for ocular gene therapy.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.