Abstract
In vivo gene editing in post-mitotic neurons of the adult brain may be a useful strategy for treating neurological diseases. Here, we develop CRISPR-Cas9 nanocomplexes and show they were effective in the adult mouse brain, with minimal off-target effects. Using this system to target Bace1 suppressed amyloid beta (Aβ)-associated pathologies and cognitive deficits in two mouse models of Alzheimer's disease. These results broaden the potential application of CRISPR-Cas9 systems to neurodegenerative diseases.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / genetics*
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Alzheimer Disease / metabolism*
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Alzheimer Disease / therapy
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Amyloid Precursor Protein Secretases / genetics*
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Amyloid Precursor Protein Secretases / metabolism
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Amyloid beta-Peptides / metabolism*
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Animals
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Aspartic Acid Endopeptidases / genetics*
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Aspartic Acid Endopeptidases / metabolism
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CRISPR-Cas Systems*
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Disease Models, Animal
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Gene Editing / methods*
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Genetic Therapy / methods
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Hippocampus / metabolism
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Male
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Mice, Transgenic
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Nanoparticles / administration & dosage
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Neurons / metabolism*
Substances
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Amyloid beta-Peptides
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Amyloid Precursor Protein Secretases
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Aspartic Acid Endopeptidases
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Bace1 protein, mouse