Gene delivery to the retina: focus on non-viral approaches

Naik, Rangeetha J.; Mukhopadhyay, Arijit; Ganguli, Munia

doi:10.1016/j.drudis.2008.09.012

Cited by 42 publications

(46 citation statements)

References 61 publications

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“…There are a number of nonviral and viral vectors that have been used successfully in retinal gene therapy proof-of-concept studies (24,25). Methods of nonviral delivery include the use of liposomes and DNA condensation reagents as vectors as well as electroporation, iontophoresis, and high-velocity cell bombardment ("gene gun").…”

Section: Gene Augmentation Therapy Considerationsmentioning

confidence: 99%

Lighting a candle in the dark: advances in genetics and gene therapy of recessive retinal dystrophies

Hollander

Black²,

Bennett³

et al. 2010

J. Clin. Invest.

184

100

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Nonsyndromic recessive retinal dystrophies cause severe visual impairment due to the death of photoreceptor and retinal pigment epithelium cells. These diseases until recently have been considered to be incurable. Molecular genetic studies in the last two decades have revealed the underlying molecular causes in approximately two-thirds of patients. The mammalian eye has been at the forefront of therapeutic trials based on gene augmentation in humans with an early-onset nonsyndromic recessive retinal dystrophy due to mutations in the retinal pigment epithelium-specific protein 65kDa (RPE65) gene. Tremendous challenges still lie ahead to extrapolate these studies to other retinal disease-causing genes, as human gene augmentation studies require testing in animal models for each individual gene and sufficiently large patient cohorts for clinical trials remain to be identified through cost-effective mutation screening protocols.

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Section: Gene Augmentation Therapy Considerationsmentioning

confidence: 99%

Lighting a candle in the dark: advances in genetics and gene therapy of recessive retinal dystrophies

Hollander

Black²,

Bennett³

et al. 2010

J. Clin. Invest.

184

100

View full text Add to dashboard Cite

show abstract

“…The well-defined anatomy and immunoprivilege of the eye are also important advantages for gene therapy (Liu et al, 2007). The small dimensions of this organ make unnecessary a high concentration of product to achieve therapeutic effects, while the diffusion from the eye into the circulation is limited (Bloquel et al, 2006;Naik et al, 2009).…”

mentioning

confidence: 99%

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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“…[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.…”

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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Gene delivery to the retina: focus on non-viral approaches

Cited by 42 publications

References 61 publications

Lighting a candle in the dark: advances in genetics and gene therapy of recessive retinal dystrophies

Lighting a candle in the dark: advances in genetics and gene therapy of recessive retinal dystrophies

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

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

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