Stieger K, Lorenz B
Klinik und Poliklinik für Augenheilkunde, Justus-Liebig-Universität Giessen, Universitätsklinikum Giessen und Marburg GmbH, Standort Giessen.
Klin Monbl Augenheilkd. 2008 Dec;225(12):1009-23. doi: 10.1055/s-2008-1027607. Epub 2008 Dec 15.
Over the last decade, significant progress has been made in the development of gene therapy strategies for the treatment of neovascular disorders and inherited dystrophies of the retina. Of all tested viral vectors, recombinant adeno-associated virus (rAAV) vectors, have been shown to be optimal vectors for gene transfer to the retina. Broadly speaking, two gene therapy strategies are used to treat retinal diseases; the first being corrective expression in the retina of the mutated gene (i. e., specific gene therapy) and the second being therapeutic expression of, for example, neurotrophic or antiangiogenic factors, in cases of neurodegenerative or neovascular, respectively, disorders (non-specific gene therapy). The naturally occurring RPE65 (-/-) Briard dog model has been successfully treated by specific gene transfer protocols and, based on these studies, the first clinical phase I trials are in preparation or have already begun. To avoid potential negative side effects due to the expression of neurotrophic and/or antiangiogenic factors in the retina, the expression of these transgenes needs to be regulated into a therapeutic window. Several regulatory systems have been tested in the retina of large animal models and may soon be used in clinical applications.
在过去十年中，用于治疗视网膜新生血管疾病和遗传性视网膜营养不良的基因治疗策略取得了重大进展。在所有经过测试的病毒载体中，重组腺相关病毒（rAAV）载体已被证明是向视网膜进行基因转移的最佳载体。广义而言，有两种基因治疗策略用于治疗视网膜疾病：第一种是在视网膜中对突变基因进行矫正表达（即特异性基因治疗），第二种是在神经退行性疾病或新生血管疾病（非特异性基因治疗）的情况下，分别对神经营养因子或抗血管生成因子进行治疗性表达。天然存在的RPE65（-/-）布里牧犬模型已通过特异性基因转移方案成功治疗，基于这些研究，首个临床I期试验正在筹备或已经开始。为避免因神经营养因子和/或抗血管生成因子在视网膜中的表达而产生潜在的负面副作用，这些转基因的表达需要被调控在一个治疗窗口内。几种调控系统已在大型动物模型的视网膜中进行了测试，可能很快会用于临床应用。
