Department of Ophthalmology, Justus-Liebig-University Giessen, Giessen, Germany.
Curr Gene Ther. 2010 Oct;10(5):389-403. doi: 10.2174/156652310793180689.
Inherited retinal diseases are non-lethal and have a wide level of genetic heterogeneity. Many of the genes involved have now been identified and their function elucidated, providing a major step towards the development of gene-based treatments. The most widely used vectors for ocular gene delivery are based on adeno-associated virus (AAV) because they mediate long-term transgene expression in a variety of retinal cell types and elicit minimal immune responses. Extensive preclinical evaluation of gene transfer strategies in small and large animal models is key to the development of successful gene-based therapies for the retina. These preclinical studies have already allowed the field to reach the point where gene therapy to treat inherited blindness has been brought to clinical trial. In this manuscript, we focus on recombinant AAV-mediated specific gene therapy for recessive retinal degenerative diseases we describe the preclinical studies for the treatment of retinal degeneration caused by retinal pigmented epithelium (RPE) cells or photoreceptor defects and the immune response induced by retinal rAAV gene transfer.
遗传性视网膜疾病是非致命性的，具有广泛的遗传异质性。现在已经确定了许多涉及的基因，并阐明了它们的功能，这为开发基于基因的治疗方法迈出了重要的一步。最广泛用于眼部基因传递的载体基于腺相关病毒（AAV），因为它们在多种视网膜细胞类型中介导长期转基因表达，并引起最小的免疫反应。在小型和大型动物模型中对基因转移策略进行广泛的临床前评估是开发成功的视网膜基因治疗的关键。这些临床前研究已经使该领域达到了可以将治疗遗传性失明的基因治疗方法推向临床试验的阶段。在本文中，我们专注于重组 AAV 介导的特定基因治疗隐性视网膜退行性疾病，我们描述了治疗由视网膜色素上皮（RPE）细胞或光感受器缺陷引起的视网膜变性和视网膜 rAAV 基因转移引起的免疫反应的临床前研究。
