Efficient genome editing in the mouse brain by local delivery of engineered Cas9 ribonucleoprotein complexes

通过局部递送工程化的 Cas9 核糖核蛋白复合物在小鼠大脑中实现高效的基因组编辑

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作者:Brett T Staahl, Madhurima Benekareddy, Claire Coulon-Bainier, Ashwin A Banfal, Stephen N Floor, Jennifer K Sabo, Cole Urnes, Gabriela Acevedo Munares, Anirvan Ghosh, Jennifer A Doudna

Abstract

We demonstrate editing of post-mitotic neurons in the adult mouse brain following injection of Cas9 ribonucleoprotein (RNP) complexes in the hippocampus, striatum and cortex. Engineered variants of Cas9 with multiple SV40 nuclear localization sequences enabled a tenfold increase in the efficiency of neuronal editing in vivo. These advances indicate the potential of genome editing in the brain to correct or inactivate the underlying genetic causes of neurological diseases.

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