Expanded repertoire of AAV vector serotypes mediate unique patterns of transduction in mouse brain.
Expanded repertoire of AAV vector serotypes mediate unique patterns of transduction in mouse brain.
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DOI：
10.1038/mt.2008.166
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发表时间：
2008-10
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影响因子：
--
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中科院分区：
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从灵长类动物组织中的潜伏基因组中发现的多种多样的腺相关病毒（AAV）结构蛋白已经扩大了AAV载体血清型的数量，这可以潜在地赋予载体独特的细胞嗜性。我们使用绿色荧光蛋白（GFP）作为报告基因在小鼠脑中评估了17个这些载体。通过新生儿侧脑室注射进行快速初步评估。选择用衣壳hu.32、hu.37、pi.2、hu.11、rh.8、hu.48R3和AAV9制备的用于比较的载体用于进一步分析，这是基于它们使大量细胞增殖并产生新的细胞转导模式的能力。这些载体被注射到成年人大脑的四个主要结构（皮层、纹状体、海马和丘脑）中，发现所有这些载体都能激活神经元。另外，hu.32、hu.11、pi.2、hu.48R3和rh.8导致GFP在一些星形胶质细胞或少突胶质细胞中表达。AAV rh.8、pi.2、hu.32和hu.11似乎也导致载体基因组的神经元转运。载体转运研究通过一个单一的单侧注射到海马和载体基因组中发现海马的投射网站。这些独特的细胞转导模式扩展了将AAV载体靶向脑细胞的选定子集的潜在库。
A wide diversity of adeno-associated virus (AAV) structural proteins uncovered from latent genomes in primate tissue has expanded the number of AAV vector serotypes, which can potentially confer unique cell tropism to the vector. We evaluated 17 of these vectors in the mouse brain using green fluorescent protein (GFP) as a reporter gene. A rapid initial evaluation was performed by neonatal lateral ventricle injections. Vectors made with capsids hu.32, hu.37, pi.2, hu.11, rh.8, hu.48R3, and AAV9 for comparison were selected for further analysis based on their ability to transduce large numbers of cells and result in novel patterns of cell transduction. These vectors were injected into adult brains in four major structures (cortex, striatum, hippocampus, and thalamus), and all were found to transduce neurons. In addition, hu.32, hu.11, pi.2, hu.48R3, and rh.8 resulted in GFP expression in some astrocytes or oligodendrocytes. AAVs rh.8, pi.2, hu.32, and hu.11 also appeared to result in neuronal transport of the vector genome. Vector transport was studied by a single unilateral injection into the hippocampus and vector genome was found in projection sites of the hippocampus. These unique patterns of cell transduction expand the potential repertoire for targeting AAV vectors to selected subsets of brain cells.
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影响因子：
12.4
作者：
Cearley, CN;Wolfe, JH
通讯作者：
Wolfe, JH
影响因子：
5.1
作者：
Liu, G;Martins, IH;Davidson, BL
通讯作者：
Davidson, BL
影响因子：
56.9
作者：
Kaspar, BK;Lladó, J;Gage, FH
通讯作者：
Gage, FH
影响因子：
5.3
作者：
Cearley, Cassia N.;Wolfe, John H.
通讯作者：
Wolfe, John H.
DOI：
10.1073/pnas.182412299
发表时间：
2002-09-03
影响因子：
11.1
作者：
Gao, GP;Alvira, MR;Wilson, JM
通讯作者：
Wilson, JM