The advent of AAV9 expands applications for brain and spinal cord gene delivery.
The advent of AAV9 expands applications for brain and spinal cord gene delivery.
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DOI：
10.1517/14712598.2012.681463
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发表时间：
2012-06
影响因子：
4.6
通讯作者：
Klein RL
中科院分区：
文献类型：
--
作者：
Dayton RD;Wang DB;Klein RL
直接研究比较了腺相关病毒（AAV）血清型，以确定最适合在CNS中稳健表达的血清型。AAV 9在直接注射到脑中时是有效的，但更令人惊讶的是，AAV 9在外周、全身途径施用给新生小鼠后在脑和脊髓中产生全局表达。主题包括AAV 9基因从脑实质内，静脉内，鞘内和子宫内给药途径的传递，以及相关的临床前研究和疾病模型。系统性AAV 9基因转移产生显著一致的神经元表达，尽管仅在早期发育中。AAV 9可用于研究神经病理学蛋白：微管相关蛋白tau和反式反应DNA结合蛋白43 kDa（TDP-43）。基于目前的数据，AAV 9将被更广泛地使用，尽管其他天然血清型和重组载体也可以支持或改善大规模表达。外周到中枢的基因传递，可以影响整个中枢神经系统，而不必注射中枢神经系统是有前途的基本功能实验，并有可能为基因治疗。如果可以在成人中实现更多的神经元表达，或者如果可以利用神经胶质表达，则应考虑全身或脑脊液内途径的AAV 9施用用于脊髓性肌萎缩症、溶酶体贮积病和肌萎缩性侧索硬化症。
Straightforward studies compared adeno-associated virus (AAV) serotypes to determine the most appropriate one for robust expression in the CNS. AAV9 was efficient when directly injected into the brain, but more surprisingly, AAV9 produced global expression in the brain and spinal cord after a peripheral, systemic route of administration to neonatal mice. Topics include AAV9 gene delivery from intraparenchymal, intravenous, intrathecal and intrauterine routes of administration, and related preclinical studies and disease models. Systemic AAV9 gene transfer yields remarkably consistent neuronal expression, though only in early development. AAV9 is versatile to study neuropathological proteins: microtubule-associated protein tau and transactive response DNA-binding protein 43 kDa (TDP-43). AAV9 will be more widely used based on current data, although other natural serotypes and recombineered vectors may also support or improve upon wide-scale expression. A peripheral-to-central gene delivery that can affect the entire CNS without having to inject the CNS is promising for basic functional experiments, and potentially for gene therapy. Systemic or intra-cerebrospinal fluid routes of AAV9 administration should be considered for spinal muscular atrophy, lysosomal storage diseases and amyotrophic lateral sclerosis, if more neuronal expression can be achieved in adults, or if glial expression can be exploited.
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影响因子：
12.4
作者：
Duque, Sandra;Joussemet, Beatrice;Barkats, Martine
通讯作者：
Barkats, Martine
影响因子：
12.4
作者：
Cearley, CN;Wolfe, JH
通讯作者：
Wolfe, JH
DOI：
10.1111/j.1440-1789.2009.01091.x
发表时间：
2010-04
期刊：
Neuropathology : official journal of the Japanese Society of Neuropathology
影响因子：
--
作者：
Geser F;Lee VM;Trojanowski JQ
通讯作者：
Trojanowski JQ
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
5.3
作者：
Dayton, Robert D.;Wang, David B.;Klein, Ronald L.
通讯作者：
Klein, Ronald L.