Combined injection of rAAV with mannitol enhances gene expression in the rat brain
Combined injection of rAAV with mannitol enhances gene expression in the rat brain
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DOI：
10.1006/mthe.2001.0246
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发表时间：
2001-02-01
影响因子：
12.4
通讯作者：
During, MJ
中科院分区：
文献类型：
--
作者：
Mastakov, MY;Baer, K;During, MJ
重组腺相关病毒（rAAV）是将基因转移到中枢神经系统（CNS）中的高效载体。然而，将基因递送至哺乳动物脑的主要障碍是在直接注射部位之外的靶细胞中实现高水平转导。因此，除了表达盒和病毒滴度的改进之外，还需要定义最佳注射参数。在这里，我们表明，以前的研究体细胞基因转移到哺乳动物的大脑使用次优注射参数，即使是最低的报告灌注率仍然过快。此外，我们评估了局部施用甘露醇以进一步增强转基因表达和载体传播的效果。rAAV的超低微灌注，即，
Recombinant adeno-associated viruses (rAAV) are highly efficient vectors for gene transfer into the central nervous system (CNS). However, a major hurdle for gene delivery to the mammalian brain is to achieve high-level transduction in target cells beyond the immediate injection site. Therefore, in addition to improvements in expression cassettes and viral titers, optimal injection parameters need to be defined. Here, we show that previous studies of somatic cell gene transfer to the mammalian brain have used suboptimal injection parameters, with even the lowest reported perfusion rates still excessively fast. Moreover, we evaluated the effect of local administration of mannitol to further enhance transgene expression and vector spread. Ultraslow microperfusion of rAAV, i.e.,