Buch P K, Bainbridge J W, Ali R R
Division of Molecular Therapy, UCL Institute of Ophthalmology and UCL/Moorfields Eye Hospital Biomedical Research Centre for Ophthalmology, London, UK.
Gene Ther. 2008 Jun;15(11):849-57. doi: 10.1038/gt.2008.66. Epub 2008 Apr 17.
A wide range of retinal disorders can potentially be treated using viral vector-mediated gene therapy. The most widely used vectors for ocular gene delivery are based on adeno-associated virus (AAV), because they elicit minimal immune responses and mediate long-term transgene expression in a variety of retinal cell types. Proof-of-concept experiments have demonstrated the efficacy of AAV-mediated transgene delivery in a number of animal models of inherited and acquired retinal disorders. Following extensive preclinical evaluation in large animal models, gene therapy for one form of inherited retinal degeneration due to RPE65 deficiency is now being tested in three concurrent clinical trials. Here, we review different approaches for treating inherited retinal degenerations and more common acquired retinal disorders using AAV-based vectors.
多种视网膜疾病都有可能通过病毒载体介导的基因疗法进行治疗。用于眼部基因递送的最广泛使用的载体是基于腺相关病毒(AAV),因为它们引发的免疫反应最小,并能在多种视网膜细胞类型中介导长期转基因表达。概念验证实验已经证明了AAV介导的转基因递送在多种遗传性和获得性视网膜疾病动物模型中的有效性。在大型动物模型中进行广泛的临床前评估后,针对一种因RPE65缺乏引起的遗传性视网膜变性的基因疗法目前正在三项同时进行的临床试验中进行测试。在这里,我们综述了使用基于AAV的载体治疗遗传性视网膜变性和更常见的获得性视网膜疾病的不同方法。