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Anti-Angiogenic Gene Therapy: Basic Science and Challenges for Translation into the Clinic

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Anti-Angiogenic Therapy in Ophthalmology

Part of the book series: Essentials in Ophthalmology ((ESSENTIALS))

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Abstract

Ocular neovascularisation is a central pathological feature of many human blinding diseases including retinopathy of prematurity, proliferative diabetic retinopathy, and age-related macular degeneration. Recent progress in understanding the molecular and cellular events involved in angiogenesis has led to the identification of powerful angiostatic molecules and the development of therapeutic approaches offering substantial benefit to affected people. However, since conventional therapeutic molecules are short-lived in the eye, sustained benefits depend on frequently repeated intraocular injections that present a significant cumulative risk of local adverse effects and a challenge for delivery of care.

Local gene transfer offers the possibility of targeted, sustained, and regulatable delivery of angiostatic proteins to the retina to provide long-term protection against harmful ocular neovascularisation and vascular leakage. Studies in animal models of retinal and choroidal neovascularisation have demonstrated significant anti-angiogenic effects after intraocular delivery of recombinant viruses carrying genes encoding angiostatic proteins. These preclinical studies have led to several ongoing clinical trials in neovascular AMD that aim to counter the chronic production of angiogenic stimuli and provide better outcomes. In this chapter, we describe the basic principles of gene therapy, review preclinical studies and clinical gene therapy trials addressing neovascular eye disease, and discuss future challenges.

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Authors and Affiliations

  1. Eye Center, University Hospital Freiburg, Killianstrasse 5, Freiburg, 79106, Germany

    Clemens Lange M.D., Ph.D.

  2. Department of Genetics, UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL, UK

    James Bainbridge Ph.D., F.R.C.Ophth.

  3. Moorfields Eye Hospital, London, UK

    James Bainbridge Ph.D., F.R.C.Ophth.

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  1. Clemens Lange M.D., Ph.D.
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  2. James Bainbridge Ph.D., F.R.C.Ophth.
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Correspondence to James Bainbridge Ph.D., F.R.C.Ophth. .

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  1. Eye Center at the Medical Center, University of Freiburg, Freiburg, Baden-Württemberg, Germany

    Andreas Stahl

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Lange, C., Bainbridge, J. (2016). Anti-Angiogenic Gene Therapy: Basic Science and Challenges for Translation into the Clinic. In: Stahl, A. (eds) Anti-Angiogenic Therapy in Ophthalmology. Essentials in Ophthalmology. Springer, Cham. https://doi.org/10.1007/978-3-319-24097-8_11

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