Ocular gene therapy: current progress and future prospects

Colella, Pasqualina; Cotugno, Gabriella; Auricchio, Alberto

doi:10.1016/j.molmed.2008.11.003

Cited by 63 publications

(57 citation statements)

References 79 publications

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“…8C and 8D). These results are in line with those obtained in a previous study in which intravitreous administration of adenoviral vectors induced protein expression in the inner retina, whereas RPE cells and outer retina were the cells primarily transfected after subretinal administration (Colella et al, 2009). This preliminary study may be useful to select the target cells to be transfected depending on the target of gene therapy.…”

Section: Discussionsupporting

confidence: 90%

Dextran and Protamine-Based Solid Lipid Nanoparticles as Potential Vectors for the Treatment of X-Linked Juvenile Retinoschisis

et al. 2012

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The goal of the present study was to analyze the potential application of nonviral vectors based on solid lipid nanoparticles (SLN) for the treatment of ocular diseases by gene therapy, specifically X-linked juvenile retinoschisis (XLRS). Vectors were prepared with SLN, dextran, protamine, and a plasmid (pCMS-EGFP or pCEP4-RS1). Formulations were characterized and the in vitro transfection capacity as well as the cellular uptake and the intracellular trafficking were studied in ARPE-19 cells. Formulations were also tested in vivo in Wistar rat eyes, and the efficacy was studied by monitoring the expression of enhanced green fluorescent protein (EGFP) after intravitreal, subretinal, and topical administration. The presence of dextran and protamine in the SLN improved greatly the expression of retinoschisin and EGFP in ARPE-19 cells. The nuclear localization signals of protamine, its ability to protect the DNA, and a shift in the entry mechanism from caveola-mediated to clathrinmediated endocytosis promoted by the dextran, justify the increase in transfection. After ocular administration of the dextran-protamine-DNA-SLN complex to rat eyes, we detected the expression of EGFP in various types of cells depending on the administration route. Our vectors were also able to transfect corneal cells after topical application. We have demonstrated the potential usefulness of our nonviral vectors loaded with XLRS1 plasmid and provided evidence for their potential application for the management or treatment of degenerative retinal disorders as well as ocular surface diseases.

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Section: Discussionsupporting

confidence: 90%

Dextran and Protamine-Based Solid Lipid Nanoparticles as Potential Vectors for the Treatment of X-Linked Juvenile Retinoschisis

et al. 2012

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“…[1] This approach has potential as both a therapy and a method for studying disease mechanisms, holding great promise for the treatment of diseases and as a proofof-principle of its efficacy in animal models and humans. [2] The ocular surface is an attractive target for gene therapy because of its immune-privileged nature and accessibility. [3] Local gene delivery has the potential to achieve low and continuous concentrations of biologically active molecules, thereby improving treatment efficacy and safety.…”

Section: Introductionmentioning

confidence: 99%

Hybrid Nanoparticle Design Based on Cationized Gelatin and the Polyanions Dextran Sulfate and Chondroitin Sulfate for Ocular Gene Therapy

Zorzi

Párraga

Seijo

et al. 2011

Macromolecular Bioscience

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We describe the development of hybrid nanoparticles composed of cationized gelatin and the polyanions CS and DS for gene therapy in the ocular surface. The physicochemical properties of the nanoparticles that impact their bioperformance, such as average size and zeta potential, can be conveniently modulated by changing the ratio of polymers and the crosslinker. These systems associate plasmid DNA and are able to protect it from DNase I degradation. We corroborate that the introduction of CS or DS in the formulation decreases the in vitro toxicity of the nanoparticles to human corneal cells without compromising the transfection efficiency. These nanoparticles are potential candidates for the development of safer and more effective nanomedicines for ocular therapy.

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“…[1][2][3] The eyes are suitable for topical gene therapy because of their accessibility, ease of monitoring, and their enclosed structure. 2,4,5) Viral vectors such as adenoviral, lentiviral, and adeno-associated virals are commonly used for ocular gene transfer [6][7][8][9] ; however, these viral vectors have some crucial problems such as toxicity, immunogenicity, possible genomic integration, limited size of inserted DNA, and difficult preparative procedures. 10,11) Therefore, non-viral vectors such as cationic polymers and cationic liposomes have been focused on because of their non-immunogenicity, low toxicity, well-defined structure, and chemical properties to yield mass production.…”

mentioning

confidence: 99%

Ocular Gene Delivery Systems Using Ternary Complexes of Plasmid DNA, Polyethylenimine, and Anionic Polymers

Kurosaki

Uematsu

Shimoda

et al. 2013

Biological & Pharmaceutical Bulletin

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In this experiment, we developed anionic ternary complexes for effective and safe ocular gene delivery. Ternary complexes were constructed by coating plasmid DNA (pDNA)/polyethylenimine (PEI) complex with anionic polymers such as γ-polyglutamic acid (γ-PGA) and chondroitin sulfate (CS). The cationic pDNA/PEI complex showed high gene expression on the human retinal pigment epithelial cell line, ARPE-19 cells. The pDNA/PEI complexes, however, also showed high cytotoxicity on the cells and aggregated strongly in the vitreous body. On the other hand, the anionic ternary complexes showed high gene expression on ARPE-19 cells without such cytotoxicity and aggregation. After intravitreous administration of the complexes, the anionic ternary complexes showed high gene expression in the retina. These results strongly indicate that anionic ternary complexes are suitable for effective and safe ocular gene therapy.

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Ocular gene therapy: current progress and future prospects

Cited by 63 publications

References 79 publications

Dextran and Protamine-Based Solid Lipid Nanoparticles as Potential Vectors for the Treatment of X-Linked Juvenile Retinoschisis

Dextran and Protamine-Based Solid Lipid Nanoparticles as Potential Vectors for the Treatment of X-Linked Juvenile Retinoschisis

Hybrid Nanoparticle Design Based on Cationized Gelatin and the Polyanions Dextran Sulfate and Chondroitin Sulfate for Ocular Gene Therapy

Ocular Gene Delivery Systems Using Ternary Complexes of Plasmid DNA, Polyethylenimine, and Anionic Polymers

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