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

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.

SUBMITTER: Staahl BT

PROVIDER: S-EPMC6649674 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Staahl Brett T BT Benekareddy Madhurima M Coulon-Bainier Claire C Banfal Ashwin A AA Floor Stephen N SN Sabo Jennifer K JK Urnes Cole C Munares Gabriela Acevedo GA Ghosh Anirvan A Doudna Jennifer A JA

Nature biotechnology 20170213 5

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. ...[more]

PMID: 28191903

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