A steroid-inducible promoter for the cornea

Parker, Douglas G.A.; Brereton, Helen M.; Klebe, Sonja; Coster, Douglas J.; Williams, Keryn A.

doi:10.1136/bjo.2009.159137

Cited by 13 publications

(10 citation statements)

References 25 publications

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“…Intensive efforts have resulted in the development of many inducible LV expression systems, such as those based on tetracycline (Tet), rapamycin, mifepristone, tamoxifen or ecdysone [35][36][37]. Of these conditional systems, the Tet-inducible system has been utilised much more frequently and have been tested successfully, from preclinical rodent models to large animal models, and in the generation of iPSCs [38][39][40].…”

Section: Transcription Regulatory Drug-inducible Lentiviral Vector Exmentioning

confidence: 99%

Optimization of Lentiviral Vectors Generation for Biomedical and Clinical Research Purposes: Contemporary Trends in Technology Development and Applications

Kumar¹,

Chan

2011

CGT

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Classical non-viral methods of gene transfer, such as chemical transfection, have met with limited success of instillation of genetic material into non-proliferating cells in vitro. Among the different kinds of viral vectors, Lentiviral vectors (LVs) have emerged as robust and versatile tool for ex vivo and in vivo gene delivery into multiple cell types including non-dividing cells such as neurons. The capacity of LVs to maintain stable, long-term transgene expression and the substantial flexibility in the design of the expression cassettes account for their increasing use in various pre-clinical and clinical applications. Additionally, LVs have been hugely successful in reprogramming induced pluripotent stem cells (iPSCs). Recent development using LVs in conjunction with a Cre-Lox based reversible system has opened up many new possibilities towards therapeutic application of iPSC technology in various clinical settings. Moreover, improvements in term of biosafety and efficacy, achieved either by modifying the vector design or by involving integration-deficient LVs (IDLVs), have important implications for adoption of LV as the vector of choice for clinical trials. Several human gene therapy clinical trials evaluating the use of LVs for treatment: of human diseases such as Parkinson's disease, β-thalassemia, X-linked adrenoleukodystrophy (ALD), and AIDS are currently ongoing. This review will describe the state of the art achieved by LV technology, its impact on biomedical research, and implications to human clinical trials as therapeutic gene delivery vehicle for a wide range of infectious and genetic diseases.

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Section: Transcription Regulatory Drug-inducible Lentiviral Vector Exmentioning

confidence: 99%

Optimization of Lentiviral Vectors Generation for Biomedical and Clinical Research Purposes: Contemporary Trends in Technology Development and Applications

Kumar¹,

Chan

2011

CGT

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“…In other cases, gene expression is regulated by drug inducible systems: expression of the protein only occurs upon administration of the corresponding inducer drug. In ocular gene therapy, this strategy has been assayed by using rapamycin [115] or doxycyclin [39] inducible systems for retinal neovascularization, or glucocorticoid response elements for glaucoma [35] or corneal transplant [116].…”

Section: Promoter Elementsmentioning

confidence: 99%

Treatment of ocular disorders by gene therapy

Solinís

Pozo-Rodríguez

Apaolaza

et al. 2015

European Journal of Pharmaceutics and Biopharmaceutics

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“…[6] Topical treatment with specific antibodies, trap proteins, or receptor antagonists has been shown to successfully prevent rejection in complicated grafts. [3334] In addition, gene therapy has been used to maintain an immunosuppressive environment in the host bed,[3536] and to inhibit the direct pathway of the antigen-presentation process by depleting antigen-presenting cells (APCs) in the donor cornea. [24]…”

Section: High-risk Corneal Transplantationmentioning

confidence: 99%

Systemic immunomodulatory strategies in high-risk corneal transplantation

Abud¹,

Zazzo²,

Kheirkhah³

et al. 2017

J Ophthalmic Vis Res

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The cornea is the most commonly transplanted tissue in the body. Although corneal grafts generally have high success rates, transplantation onto inflamed and vascularized host beds, or so-called high-risk corneal transplantation, has a high rate of graft rejection. The management of this high-risk corneal transplantation is challenging and involves numerous measures. One of the key measures to prevent graft rejection in these cases is the use of systemic immunosuppressive agents. In this article, we will review the systemic immunosuppressive agents most commonly used for high-risk corneal transplantation, which include corticosteroids, cysclosporine A, tacrolimus, mycophenolate mofetil, and rapamycin. Benefits, risks, and published data on the use of these medications for high-risk corneal transplantation will be detailed. We will also summarize novel immunoregulatory approaches that may be used to prevent graft rejection in high-risk corneal transplantation.

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A steroid-inducible promoter for the cornea

Abstract: The GRE5 promoter in a lentiviral vector drove rapid, sustained and inducible transgene expression in both ovine and human corneas in the presence of dexamethasone. A steroid-inducible promoter may be useful for controlling transgene expression in gene-modified donor corneal allografts.

Cited by 13 publications

References 25 publications

Optimization of Lentiviral Vectors Generation for Biomedical and Clinical Research Purposes: Contemporary Trends in Technology Development and Applications

Optimization of Lentiviral Vectors Generation for Biomedical and Clinical Research Purposes: Contemporary Trends in Technology Development and Applications

Treatment of ocular disorders by gene therapy

Systemic immunomodulatory strategies in high-risk corneal transplantation

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