Transduction characteristics of adeno-associated virus vectors expressing cap serotypes 7, 8, 9, and Rh10 in the mouse brain
Transduction characteristics of adeno-associated virus vectors expressing cap serotypes 7, 8, 9, and Rh10 in the mouse brain
复制标题
DOI：
10.1016/j.ymthe.2005.11.015
复制
发表时间：
2006-03-01
影响因子：
12.4
通讯作者：
Wolfe, JH
中科院分区：
文献类型：
--
作者：
Cearley, CN;Wolfe, JH
重组腺相关病毒（AAV）载体可以转染CNS细胞，导致长期表达。AAV载体转导根据所用血清型和注射的脑区域而变化。AAV血清型7、8、9和RHO最近已变得可用，但这些血清型在CNS内的转导能力尚未确定。我们表明，AAV 7，8，9，和Rh 10载体表达的溶酶体酶的cDNA transluce神经元，但不是星形胶质细胞或少突胶质细胞，在皮层，纹状体，海马和丘脑。尽管所有载体都含有相同的基因组，但存在明显不同的转导模式，这可能仅是由于衣壳蛋白的差异。发现AAV 9载体通过已知的轴突途径经历载体基因组转运至远端神经元细胞体。这促进了酶的分布，导致在患病大脑的区域中的溶酶体储存损伤的校正，如果基因组不被运输，这些损伤将不会被校正。
Recombinant adeno-associated viral (AAV) vectors can transduce cells of the CNS, resulting in longterm expression. AAV vector transduction varies depending on the serotype used and the region of the brain injected. AAV serotypes 7, 8, 9, and RHO have recently become available, but the transduction capabilities of these serotypes within the CNS have not been determined. We show that AAV 7, 8, 9, and Rh 10 vectors expressing cDNA for a lysosomal enzyme transcluce neurons, but not astrocytes or oligodendrocytes, in the cortex, striatum, hippocampus, and thalamus. Although all of the vectors contained the same genome, there were markedly different transduction patterns that could be due only to the differences in capsid proteins. The AAV 9 vector was found to undergo vector genome transport to distal neuronal cell bodies via known axonal pathways. This facilitated the distribution of enzyme, resulting in correction of lysosomal storage lesions in regions of a diseased brain that would not be corrected if the genome were not transported.