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The Self-Inactivating KamiCas9 System for the Editing of CNS Disease Genes.
Merienne, Nicolas; Vachey, Gabriel; de Longprez, Lucie; Meunier, Cécile; Zimmer, Virginie; Perriard, Guillaume; Canales, Mathieu; Mathias, Amandine; Herrgott, Lucas; Beltraminelli, Tim; Maulet, Axelle; Dequesne, Thomas; Pythoud, Catherine; Rey, Maria; Pellerin, Luc; Brouillet, Emmanuel; Perrier, Anselme L; du Pasquier, Renaud; Déglon, Nicole.
Afiliación
  • Merienne N; Department of Clinical Neurosciences, Laboratory of Cellular and Molecular Neurotherapies (LCMN), Lausanne University Hospital, 1011 Lausanne, Switzerland; Neurosciences Research Center (CRN), LCMN, Lausanne University Hospital, 1011 Lausanne, Switzerland.
  • Vachey G; Department of Clinical Neurosciences, Laboratory of Cellular and Molecular Neurotherapies (LCMN), Lausanne University Hospital, 1011 Lausanne, Switzerland; Neurosciences Research Center (CRN), LCMN, Lausanne University Hospital, 1011 Lausanne, Switzerland.
  • de Longprez L; CEA, DRF, Institut François Jacob, Molecular Imaging Research Center (MIRCen), F-92265 Fontenay-aux-Roses, France; Neurodegenerative Diseases Laboratory, CNRS, CEA, Université Paris-Sud, Université Paris-Saclay (UMR9199), F-92265 Fontenay-aux-Roses, France.
  • Meunier C; Department of Physiology, Laboratory of Neuroenergetics, University of Lausanne, 1011 Lausanne, Switzerland.
  • Zimmer V; Department of Clinical Neurosciences, Laboratory of Cellular and Molecular Neurotherapies (LCMN), Lausanne University Hospital, 1011 Lausanne, Switzerland; Neurosciences Research Center (CRN), LCMN, Lausanne University Hospital, 1011 Lausanne, Switzerland.
  • Perriard G; Department of Clinical Neurosciences, Laboratory of Neuro-immunology, Lausanne University Hospital, 1011 Lausanne, Switzerland; Neurosciences Research Center (CRN), Laboratory of Neuro-immunology, Lausanne University Hospital, 1011 Lausanne, Switzerland.
  • Canales M; Department of Clinical Neurosciences, Laboratory of Neuro-immunology, Lausanne University Hospital, 1011 Lausanne, Switzerland; Neurosciences Research Center (CRN), Laboratory of Neuro-immunology, Lausanne University Hospital, 1011 Lausanne, Switzerland.
  • Mathias A; Department of Clinical Neurosciences, Laboratory of Neuro-immunology, Lausanne University Hospital, 1011 Lausanne, Switzerland; Neurosciences Research Center (CRN), Laboratory of Neuro-immunology, Lausanne University Hospital, 1011 Lausanne, Switzerland.
  • Herrgott L; Department of Clinical Neurosciences, Laboratory of Cellular and Molecular Neurotherapies (LCMN), Lausanne University Hospital, 1011 Lausanne, Switzerland; Neurosciences Research Center (CRN), LCMN, Lausanne University Hospital, 1011 Lausanne, Switzerland.
  • Beltraminelli T; Department of Clinical Neurosciences, Laboratory of Cellular and Molecular Neurotherapies (LCMN), Lausanne University Hospital, 1011 Lausanne, Switzerland; Neurosciences Research Center (CRN), LCMN, Lausanne University Hospital, 1011 Lausanne, Switzerland.
  • Maulet A; Institut National de la Santé et de la Recherche Médicale (INSERM) UMR861, I-Stem, AFM, 91100 Corbeil-Essonnes, France.
  • Dequesne T; Department of Clinical Neurosciences, Laboratory of Cellular and Molecular Neurotherapies (LCMN), Lausanne University Hospital, 1011 Lausanne, Switzerland; Neurosciences Research Center (CRN), LCMN, Lausanne University Hospital, 1011 Lausanne, Switzerland.
  • Pythoud C; Department of Clinical Neurosciences, Laboratory of Cellular and Molecular Neurotherapies (LCMN), Lausanne University Hospital, 1011 Lausanne, Switzerland; Neurosciences Research Center (CRN), LCMN, Lausanne University Hospital, 1011 Lausanne, Switzerland.
  • Rey M; Department of Clinical Neurosciences, Laboratory of Cellular and Molecular Neurotherapies (LCMN), Lausanne University Hospital, 1011 Lausanne, Switzerland; Neurosciences Research Center (CRN), LCMN, Lausanne University Hospital, 1011 Lausanne, Switzerland.
  • Pellerin L; Department of Physiology, Laboratory of Neuroenergetics, University of Lausanne, 1011 Lausanne, Switzerland.
  • Brouillet E; CEA, DRF, Institut François Jacob, Molecular Imaging Research Center (MIRCen), F-92265 Fontenay-aux-Roses, France; Neurodegenerative Diseases Laboratory, CNRS, CEA, Université Paris-Sud, Université Paris-Saclay (UMR9199), F-92265 Fontenay-aux-Roses, France.
  • Perrier AL; Institut National de la Santé et de la Recherche Médicale (INSERM) UMR861, I-Stem, AFM, 91100 Corbeil-Essonnes, France.
  • du Pasquier R; Department of Clinical Neurosciences, Laboratory of Neuro-immunology, Lausanne University Hospital, 1011 Lausanne, Switzerland; Neurosciences Research Center (CRN), Laboratory of Neuro-immunology, Lausanne University Hospital, 1011 Lausanne, Switzerland; Service of Neurology, Department of Clinical
  • Déglon N; Department of Clinical Neurosciences, Laboratory of Cellular and Molecular Neurotherapies (LCMN), Lausanne University Hospital, 1011 Lausanne, Switzerland; Neurosciences Research Center (CRN), LCMN, Lausanne University Hospital, 1011 Lausanne, Switzerland. Electronic address: nicole.deglon@chuv.ch.
Cell Rep ; 20(12): 2980-2991, 2017 Sep 19.
Article en En | MEDLINE | ID: mdl-28930690
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Enfermedades del Sistema Nervioso Central / Sistemas CRISPR-Cas / Edición Génica Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2017 Tipo del documento: Article País de afiliación: Suiza
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Enfermedades del Sistema Nervioso Central / Sistemas CRISPR-Cas / Edición Génica Límite: Animals / Humans Idioma: En Revista: Cell Rep Año: 2017 Tipo del documento: Article País de afiliación: Suiza