| Literature DB >> 28930690 |
Nicolas Merienne1, Gabriel Vachey1, Lucie de Longprez2, Cécile Meunier3, Virginie Zimmer1, Guillaume Perriard4, Mathieu Canales4, Amandine Mathias4, Lucas Herrgott1, Tim Beltraminelli1, Axelle Maulet5, Thomas Dequesne1, Catherine Pythoud1, Maria Rey1, Luc Pellerin3, Emmanuel Brouillet2, Anselme L Perrier5, Renaud du Pasquier6, Nicole Déglon7.
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.Entities:
Keywords: CRISPR/Cas9; Huntington’s disease; KamiCas9; gene editing; lentiviral vectors; neurodegenerative diseases; self-inactivating system
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Year: 2017 PMID： 28930690 DOI： 10.1016/j.celrep.2017.08.075
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423