Efficient gene transfer into neurons in monkey brain by adeno-associated virus 8

Efficient gene transfer into neurons in monkey brain by adeno-associated virus 8
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DOI:
10.1097/wnr.0b013e328338ba00
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发表时间:
2010-04-21
期刊:
影响因子:
1.7
通讯作者:
Nakahara, Kiyoshi
Nakahara, Kiyoshi
中科院分区:
医学4区
文献类型:
--
作者:
Masamizu, Yoshito;Okada, Takashi;Nakahara, Kiyoshi

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尽管腺相关病毒 (AAV) 载体是将基因转移到神经元中的一种很有前途的工具,特别是用于治疗目的,但灵长类动物大脑中特定 AAV 血清型的向神经性尚未完全阐明。在这里,我们将携带增强型绿色荧光蛋白(EGFP)基因的 AAV 血清型 8(AAV8)载体注射到普通狨猴的大脑皮层、纹状体和黑质中。在所有注射部位均观察到强健的神经元 EGFP 表达。免疫组织化学细胞分型证实 AAV8 介导的基因有效转移到皮质中的锥体神经元、纹状体中的钙结合蛋白阳性中型多棘神经元和黑质中的多巴胺能神经元中。结果表明,AAV8 对猴脑中的神经元亚群具有偏向性,但对神经胶质细胞没有偏向性。 NeuroReport 21:447-451 (C) 2010 Wolters Kluwer Health |利平科特·威廉姆斯和威尔金斯。
Although the adeno-associated virus (AAV) vector is a promising tool for gene transfer into neurons, especially for therapeutic purposes, neurotropism in primate brains is not fully elucidated for specific AAV serotypes. Here, we injected AAV serotype 8 (AAV8) vector carrying the enhanced green fluorescent protein (EGFP) gene under a ubiquitous promoter into the cerebral cortex, striatum and substantia nigra of common marmosets. Robust neuronal EGFP expression was observed at all injected sites. Cell typing with immunohistochemistry confirmed efficient AAV8-mediated gene transfer into the pyramidal neurons in the cortex, calbindin-positive medium spiny neurons in the striatum and dopaminergic neurons in the substantia nigra. The results indicate a preferential tropism of AAV8 for subsets of neurons, but not for glia, in monkey brains. NeuroReport 21: 447-451 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.