Analysis of transduction efficiency, tropism and axonal transport of AAV serotypes 1, 2, 5, 6, 8 and 9 in the mouse brain.
Analysis of transduction efficiency, tropism and axonal transport of AAV serotypes 1, 2, 5, 6, 8 and 9 in the mouse brain.
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DOI：
10.1371/journal.pone.0076310
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Rumpel S
中科院分区：
文献类型：
--
作者：
Aschauer DF;Kreuz S;Rumpel S
重组腺相关病毒载体（rAAV）广泛用于基因传递，多种天然存在的血清型已被用来靶向包括大脑在内的不同组织和器官的细胞。在这里，我们基于六种最常用的血清型（AAV1、AAV2、AAV5、AAV6、AAV8、AAV9）对 rAAV 载体的转导谱进行了详细的定量分析，以便系统地比较和选择特定应用的最佳载体。在我们的研究中，我们观察到血清型之间转导三个不同大脑区域（即小鼠纹状体、海马体和新皮质）的效率存在显着差异。尽管所分析的血清型具有转导大脑中所有主要细胞类型（神经元、小胶质细胞、星形胶质细胞和少突胶质细胞）的一般能力，但由普遍存在的启动子驱动的报告基因的表达水平对于特定细胞类型/血清型组合存在显着差异。例如，rAAV8 对于驱动星形胶质细胞中的转基因表达特别有效，而 rAAV9 似乎非常适合皮层神经元的转导。有趣的是，我们证明了rAAV5沿着从内嗅皮层腹侧部分投射到齿状回的轴突选择性逆行运输。此外，我们还发现，自我补充的 rAAV 可用于显着缩短小鼠大脑中转基因表达开始所需的时间。
Recombinant Adeno-associated virus vectors (rAAV) are widely used for gene delivery and multiple naturally occurring serotypes have been harnessed to target cells in different tissues and organs including the brain. Here, we provide a detailed and quantitative analysis of the transduction profiles of rAAV vectors based on six of the most commonly used serotypes (AAV1, AAV2, AAV5, AAV6, AAV8, AAV9) that allows systematic comparison and selection of the optimal vector for a specific application. In our studies we observed marked differences among serotypes in the efficiency to transduce three different brain regions namely the striatum, hippocampus and neocortex of the mouse. Despite the fact that the analyzed serotypes have the general ability to transduce all major cell types in the brain (neurons, microglia, astrocytes and oligodendrocytes), the expression level of a reporter gene driven from a ubiquitous promoter varies significantly for specific cell type / serotype combinations. For example, rAAV8 is particularly efficient to drive transgene expression in astrocytes while rAAV9 appears well suited for the transduction of cortical neurons. Interestingly, we demonstrate selective retrograde transport of rAAV5 along axons projecting from the ventral part of the entorhinal cortex to the dentate gyrus. Furthermore, we show that self-complementing rAAV can be used to significantly decrease the time required for the onset of transgene expression in the mouse brain.
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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：
5.4
作者：
Akache, Bassel;Grimm, Dirk;Kay, Mark A.
通讯作者：
Kay, Mark A.
影响因子：
4.8
作者：
Fitzsimons, HL;Bland, RJ;During, MJ
通讯作者：
During, MJ
影响因子：
5.4
作者：
Ferrari, FK;Samulski, T;Samulski, RJ
通讯作者：
Samulski, RJ
DOI：
10.1073/pnas.0603081103
发表时间：
2006-06-06
影响因子：
11.1
作者：
Hnasko, Thomas S.;Perez, Francisco A.;Palmiter, Richard D.
通讯作者：
Palmiter, Richard D.