Despite rapid progresses in the genome-editing field, in vivo simultaneous overexpression of multiple genes remains challenging. We generated a transgenic mouse using an improved dCas9 system that enables simultaneous and precise in vivo transcriptional activation of multiple genes and long noncoding RNAs in the nervous system. As proof of concept, we were able to use targeted activation of endogenous neurogenic genes in these transgenic mice to directly and efficiently convert astrocytes into functional neurons in vivo. This system provides a flexible and rapid screening platform for studying complex gene networks and gain-of-function phenotypes in the mammalian brain.

中文翻译：

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使用CRISPR-dCas9-activator转基因小鼠体内多种基因的体内同时转录激活。

尽管在基因组编辑领域中取得了快速进展，但是体内同时表达多种基因仍然具有挑战性。我们使用改进的dCas9系统生成了转基因小鼠，该系统能够同时精确地在神经系统中对多个基因和长非编码RNA进行体内转录激活。作为概念的证明，我们能够在这些转基因小鼠中使用内源性神经源性基因的靶向激活，以在体内直接有效地将星形胶质细胞转化为功能性神经元。该系统提供了一个灵活而快速的筛选平台，用于研究哺乳动物脑中的复杂基因网络和功能获得表型。