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

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Version: Final published version
License: Not specified
Serval ID
serval:BIB_18C9D3A78F11
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The Self-Inactivating KamiCas9 System for the Editing of CNS Disease Genes.
Journal
Cell reports
Author(s)
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 A.L., du Pasquier R., Déglon N.
ISSN
2211-1247 (Electronic)
Publication state
Published
Issued date
19/09/2017
Peer-reviewed
Oui
Volume
20
Number
12
Pages
2980-2991
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
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.
Keywords
Animals, Astrocytes/cytology, Astrocytes/metabolism, Base Sequence, CRISPR-Cas Systems/genetics, Cells, Cultured, Central Nervous System Diseases/genetics, Cerebral Cortex/cytology, Gene Editing, HEK293 Cells, Humans, Huntingtin Protein/genetics, Induced Pluripotent Stem Cells/cytology, Induced Pluripotent Stem Cells/metabolism, Kinetics, Mice, Neurons/cytology, Neurons/metabolism, CRISPR/Cas9, Huntington’s disease, KamiCas9, gene editing, lentiviral vectors, neurodegenerative diseases, self-inactivating system
Pubmed
Web of science
Open Access
Yes
Create date
05/10/2017 7:55
Last modification date
19/06/2020 5:21
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