Journal
CELL REPORTS
Volume 20, Issue 12, Pages 2980-2991Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2017.08.075
Keywords
-
Categories
Funding
- Swiss National Science Foundation [31003A-165834]
- Association Francaise contre les Myopathies (AFM-Telethon)
- Agence Nationale pour la Recherche, Neuratris [ANR-11-INBS-0011]
- Laboratoire d'Excellence Revive (Investissement d'Avenir) [ANR-10-LABX-73]
- French National Health Institute (INSERM)
- Novartis Foundation
- EU Joint Programme-Neurodegenerative Disease Research (JPND) [643417]
- aegis of JPND (France, French National Research Agency [ANR])
- aegis of JPND (Switzerland, State Secretariat for Education, Research, and Innovation [SERI])
- aegis of JPND (Swiss National Science Foundation) [FN 31ND30-166947/1]
- Fondation pour la Recherche Medicale
- Swiss National Science Foundation (SNF) [31003A_165834] Funding Source: Swiss National Science Foundation (SNF)
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available