AAV-mediated gene therapy in mouse models of recessive retinal degeneration.
AAV-mediated gene therapy in mouse models of recessive retinal degeneration.
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DOI：
10.2174/156652412799218877
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发表时间：
2012-03
影响因子：
2.5
通讯作者：
McDowell JH
中科院分区：
文献类型：
--
作者：
Pang JJ;Lei L;Dai X;Shi W;Liu X;Dinculescu A;McDowell JH
近年来，越来越多的引起视网膜疾病的突变基因被发现。同时，也发现了许多自然发生的视网膜变性小鼠模型，它们表现出与人类视网膜疾病相似的变化。随着病毒载体质量的提高，越来越多传统上无法治愈的遗传性视网膜疾病成为基因治疗的潜在候选者。目前，将治疗性基因传递到靶视网膜细胞的最常见载体是腺相关病毒载体（AAV）。在将aav载体传递到具有免疫特权的视网膜下间隙后，aav载体可以有效地靶向视网膜色素上皮和光感受器细胞，这是大多数视网膜变性的起源。本文综述了基于aav的基因治疗在小鼠隐性视网膜变性模型中的应用，特别是那些通过形态学、生化、视网膜电图和行为分析确定的野生型基因正确拷贝的传递对视觉功能有显著有益影响的小鼠模型。过去的动物模型研究和正在进行的成功的LCA2临床试验，预测了AAV基因替代治疗遗传性隐性视网膜疾病的光明前景。
In recent years, more and more mutant genes that cause retinal diseases have been detected. At the same time, many naturally occurring mouse models of retinal degeneration have also been found, which show similar changes to human retinal diseases. These, together with improved viral vector quality allow more and more traditionally incurable inherited retinal disorders to become potential candidates for gene therapy. Currently, the most common vehicle to deliver the therapeutic gene into target retinal cells is the adeno-associated viral vector (AAV). Following delivery to the immuno-priviledged subretinal space, AAV-vectors can efficiently target both retinal pigment epithelium and photoreceptor cells, the origin of most retinal degenerations. This review focuses on the AAV-based gene therapy in mouse models of recessive retinal degenerations, especially those in which delivery of the correct copy of the wild-type gene has led to significant beneficial effects on visual function, as determined by morphological, biochemical, electroretinographic and behavioral analysis. The past studies in animal models and ongoing successful LCA2 clinical trials, predict a bright future for AAV gene replacement treatment for inherited recessive retinal diseases.
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影响因子：
4.2
作者：
Cideciyan, Artur V.;Hauswirth, William W.;Jacobson, Samuel G.
通讯作者：
Jacobson, Samuel G.
影响因子：
4.4
作者：
Allocca, Mariacarmela;Manfredi, Anna;Auricchio, Alberto
通讯作者：
Auricchio, Alberto
DOI：
10.1073/pnas.96.13.7553
发表时间：
1999-06-22
影响因子：
11.1
作者：
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通讯作者：
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作者：
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通讯作者：
Palczewski, K
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4
作者：
Aligianis, IA;Forshew, T;Maher, ER
通讯作者：
Maher, ER