Gene delivery to the eye using adeno-associated viral vectors
Gene delivery to the eye using adeno-associated viral vectors
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DOI：
10.1016/s1046-2023(02)00232-3
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发表时间：
2002-10-01
期刊：
影响因子：
4.8
通讯作者：
Quigley, HA
中科院分区：
文献类型：
--
作者：
Martin, KRG;Klein, RL;Quigley, HA
腺相关病毒（AAV）载体提供了一种有用的方式将基因传递到眼睛。它们具有许多重要的特性，使它们适合于此目的。尤其是它们缺乏显著的致病性和长期转染视网膜细胞的潜力。用于AAV介导的基因递送的最佳方法由靶细胞类型的位置和特征决定。在视网膜下注射AAV后，已经在各种动物模型中实现了向光感受器和色素上皮细胞的有效基因递送。AAV介导的基因治疗已显示在原发性光感受器疾病的啮齿动物模型中和在患有类似于人Leber先天性黑蒙（LCA）的自然发生的疾病的狗中减缓光感受器损失。然而，向其他细胞类型如视网膜神经节细胞（RGC）的有效基因递送一直是更成问题的。在这篇文章中。我们回顾了AAV介导的基因递送到眼睛的潜在用途。我们描述了选择合适的AAV载体用于眼部基因转移研究，并讨论了用于将病毒递送至眼部并评估眼部转染的技术。我们将我们的技术成功地转移到视网膜神经节细胞，这通常被证明是具有挑战性的，以高效率。使用并入鸡P-肌动蛋白（CBA）启动子和土拨鼠肝炎转录后调控元件的经修饰的AAV。我们描述了我们的技术如何允许在单次玻璃体内病毒注射的2周内转染大约85%的大鼠视网膜神经节细胞。我们的技术促进了对RGC疾病（如青光眼）发病机制的研究，以及基于基因治疗的新型治疗方法的开发。(C)2002 Elsevier Science（美国）。All rights reserved.
Adeno-associated virus (AAV) vectors provide a useful way to deliver genes to the eye. They have a number of important properties which make them Suitable for this purpose. not least their lack of significant pathogenicity and the potential for long-term transfection of retinal cells. The optimal methods for AAV-mediated gene delivery are determined by the location and characteristics of the target cell type. Efficient gene delivery to photoreceptors and pigment epithelial cells following subretinal injection of AAV has been achieved in various animal models. AAV-mediated gene therapy has been shown to slow photoreceptor loss in rodent models of primary photoreceptor diseases and in dogs with a naturally occurring disease similar to human Leber's congenital amaurosis (LCA). Efficient gene delivery to other cell types such as retinal ganglion cells (RGCs), however, has been more problematic. In this article. we review the potential uses of AAV-mediated gene delivery to the eye. We describe the selection of an appropriate AAV vector for ocular gene transfer studies and discuss the techniques used to deliver the virus to the eye and to assess ocular transfection. We erriphasize Our techniques for successful gene transfer to retinal ganglion cells, which have often proven challenging to transfect with high efficiency. Using a modified AAV incorporating a chicken P-actin (CBA) promoter and the woodchuck hepatitis post transcriptional regulatory element. we describe how, our techniques allow approximately 85% of rat retinal ganglion cells to be transfected within 2 weeks of a single intravitreal virus injection. Our techniques facilitate the study of the pathogenesis of RGC diseases Such as glaucoma and the development of novel new treatments based on gene therapy. (C) 2002 Elsevier Science (USA). All rights reserved.