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病毒靶向中枢和外周神经系统的策略。

Viral Strategies for Targeting the Central and Peripheral Nervous Systems.

机构信息

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA; email:

出版信息

Annu Rev Neurosci. 2018 Jul 8;41:323-348. doi: 10.1146/annurev-neuro-080317-062048. Epub 2018 Apr 25.

DOI:10.1146/annurev-neuro-080317-062048
PMID:29709207
Abstract

Recombinant viruses allow for targeted transgene expression in specific cell populations throughout the nervous system. The adeno-associated virus (AAV) is among the most commonly used viruses for neuroscience research. Recombinant AAVs (rAAVs) are highly versatile and can package most cargo composed of desired genes within the capsid's ∼5-kb carrying capacity. Numerous regulatory elements and intersectional strategies have been validated in rAAVs to enable cell type-specific expression. rAAVs can be delivered to specific neuronal populations or globally throughout the animal. The AAV capsids have natural cell type or tissue tropism and trafficking that can be modified for increased specificity. Here, we describe recently engineered AAV capsids and associated cargo that have extended the utility of AAVs in targeting molecularly defined neurons throughout the nervous system, which will further facilitate neuronal circuit interrogation and discovery.

摘要

重组病毒可在神经系统的特定细胞群体中实现靶向转基因表达。腺相关病毒 (AAV) 是神经科学研究中最常用的病毒之一。重组腺相关病毒 (rAAV) 具有高度通用性,可以将大多数由衣壳的约 5kb 载体内所需基因组成的有效载荷进行包装。许多调控元件和交叠策略已在 rAAV 中得到验证,以实现细胞类型特异性表达。rAAV 可递送至特定神经元群体或整个动物体内。AAV 衣壳具有天然的细胞类型或组织趋向性和运输特性,可通过修饰来提高特异性。在这里,我们描述了最近设计的 AAV 衣壳及其相关载体,它们扩展了 AAV 在靶向神经系统中分子定义神经元中的应用,这将进一步促进神经元回路的检测和发现。

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