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The Self-Inactivating KamiCas9 System for the Editing of CNS Disease Genes.

Abstract：

:Neurodegenerative disorders are a major public health problem because of the high frequency of these diseases. Genome editing with the CRISPR/Cas9 system is making it possible to modify the sequence of genes linked to these disorders. We designed the KamiCas9 self-inactivating editing system to achieve transient expression of the Cas9 protein and high editing efficiency. In the first application, the gene responsible for Huntington's disease (HD) was targeted in adult mouse neuronal and glial cells. Mutant huntingtin (HTT) was efficiently inactivated in mouse models of HD, leading to an improvement in key markers of the disease. Sequencing of potential off-targets with the constitutive Cas9 system in differentiated human iPSC revealed a very low incidence with only one site above background level. This off-target frequency was significantly reduced with the KamiCas9 system. These results demonstrate the potential of the self-inactivating CRISPR/Cas9 editing for applications in the context of neurodegenerative diseases.

journal_name

Cell Rep

journal_title

Cell reports

authors

Merienne N,Vachey G,de Longprez L,Meunier C,Zimmer V,Perriard G,Canales M,Mathias A,Herrgott L,Beltraminelli T,Maulet A,Dequesne T,Pythoud C,Rey M,Pellerin L,Brouillet E,Perrier AL,du Pasquier R,Déglon N

doi

10.1016/j.celrep.2017.08.075

subject

Has Abstract

pub_date

2017-09-19 00:00:00

pages

2980-2991

issue

12

issn

2211-1247

pii

S2211-1247(17)31217-2

journal_volume

20

pub_type

杂志文章

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