Ocular gene therapy: A review of non-viral strategies

Andrieu-Soler, Charlotte; Bejjani, R.A.; Bizemont, Thérèse de; Normand, Nadia; Benezra, Diane; Behar-Cohen, F

doi:10.1016/j.ajo.2007.02.011

Cited by 29 publications

(37 citation statements)

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“…The efficiency and duration of expression of non-viral vectors, which can transduce a wide range of ocular cell types, can be improved considerably by electrotransfer and iontophoresis. 2,3 Adenoviral vectors efficiently target cells of the outer retina 4,5 but their duration of expression is limited by immune responses to the vector. 6 Newer, helper-dependent Ad vectors may mediate longer-term expression.…”

Section: Introductionmentioning

confidence: 99%

Prospects for gene therapy of inherited retinal disease

Bainbridge

2009

Eye

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Gene-based therapies offer the means to address gene defects responsible for inherited retinal disorders. A number of studies in experimental and preclinical models have demonstrated proof-of-principle that gene replacement therapy can mediate significant quantifiable improvements in ocular morphology and visual function. The first results of clinical trials of gene therapy for early-onset severe retinal dystrophy caused by defects in RPE65 show proof-of-concept for efficacy and short-term safety in humans. The challenges for gene therapy of conditions caused by gain-of-abnormal function are being addressed by strategies to knock down expression of the disease allele. Vector-mediated expression of neuroprotective proteins may offer a generic approach for preserving vision in single-gene and multi-gene retinal degenerations. Gene therapy is likely to be most successful where stable expression of the therapeutic transgene can be achieved at an appropriate level in diseases in which retinal development is unaffected and a significant number of target cells survive at the point of intervention.

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Section: Introductionmentioning

confidence: 99%

Prospects for gene therapy of inherited retinal disease

Bainbridge

2009

Eye

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“…Another advantage for retinal gene therapy is that the target cell populations are typically very stable. The lack of cell division allows the use of non-integrating vector systems, whether viral (for example, recombinant adeno-associated virus (AAV) 1 or non-integrating lentivirus 2 ) or non-viral, 3 for sustained transgene expression. As insertion of the vector genome into the host cell genome is associated with insertional mutagenesis and oncogenesis, 4 the use of non-integrating systems could substantially reduce the possibility of malignant transformation of the target cells.…”

Section: Inherited Retinal Degeneration As a Target For Gene Therapymentioning

confidence: 99%

“…Photoreceptor cell transduction or transfection by early adenovirus, 11 HIV-based lentiviruses 12,13 or various non-viral methods 3 is relatively inefficient, and the duration of transgene expression limited either by silencing of the transgene promoter 14 or through clearance of transduced cells after immune responses to vector proteins. 15 Further development of these vector systems, for example, by the removal of immunogenic viral genes from the vector genome of adenovirus 16 or the removal of bacterial plasmid sequences in DNA mini-circles in non-viral gene transfer 17 has resulted in significant improvements in longevity of expression.…”

Section: Gene Transfer To Photoreceptor Cellsmentioning

confidence: 99%

Gene supplementation therapy for recessive forms of inherited retinal dystrophies

Smith¹,

Bainbridge²,

Ali³

2011

Gene Ther

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Over the last decade, gene supplementation therapy for inherited retinal degeneration has come of age. Early proof-of-concept studies in animal models of disease showed modest, but genuine improvements in retinal function and/or survival. Further development of the vectors used for gene transfer to the retina has led to better treatment efficacy in a wide variety of animal models, leading in 2008 to the initiation of three clinical trials for Leber congenital amaurosis caused by retinal pigment epithelium 65 deficiency. The results from these trials suggest that the treatment of inherited retinal dystrophy by gene therapy can be safe and effective. Here, we examine the progress of gene supplementation therapy in the retina, and discuss the potential for using gene therapy to treat different forms of inherited retinal degeneration.

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“…In addition, the presence of physical barriers in the eye, such as the vitreous, inner/outer limiting membranes, the inter-PR matrix, and the high concentrations of glycosaminoglycans present throughout the eye that sequester the DNA, further limit cellular access (Lipinski et al 2013). As a consequence, many studies have provided evidence of the higher efficiency of viral versus nonviral retinal gene delivery (Andrieu-Soler et al 2006). In particular, injection of naked DNA via subretinal injection between the PR and retinal pigment epithelium (RPE) (Liang et al 2000) is highly inefficient (Charbel Issa and MacLaren 2012).…”

Section: Nonviral Gene Delivery In Abca4-associated Diseasesmentioning

confidence: 99%

Gene Therapy of ABCA4-Associated Diseases

Auricchio

Trapani

Allikmets

2015

Cold Spring Harbor Perspectives in Medicine

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The ATP-binding cassette (ABC) transporter gene, ABCA4 (ABCR), was characterized in 1997 as the causal gene for autosomal recessive Stargardt disease (STGD1). Shortly thereafter several other phenotypes were associated with mutations in ABCA4, which now have collectively emerged as the most frequent cause of retinal degeneration phenotypes of Mendelian inheritance. ABCA4 functions as an important transporter (or "flippase") of vitamin A derivatives in the visual cycle. Several ways to alleviate the effects of the defective ABCA4 protein, which cause accumulation of 11-cis and all-trans-retinal in photoreceptors and lipofuscin in the retinal pigment epithelium, have been proposed. Although ABCA4 has proven to be a difficult research target, substantial progress through genetic, functional, and translational studies has allowed major advances in therapeutic applications for ABCA4-associated pathology, which should be available to patients in the (near) future. Here, we summarize the status of the gene therapy-based treatment options of ABCA4-associated diseases.

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Ocular gene therapy: A review of non-viral strategies

Cited by 29 publications

References 0 publications

Prospects for gene therapy of inherited retinal disease

Prospects for gene therapy of inherited retinal disease

Gene supplementation therapy for recessive forms of inherited retinal dystrophies

Gene Therapy of ABCA4-Associated Diseases

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