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| Status |
Public on Mar 09, 2020 |
| Title |
In vivo delivery of CRISPR/Cas9 nanocomplexes in post-mitotic neurons for Alzheimer’s disease therapy |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Other
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| Summary |
The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system has emerged as a powerful technique for correcting genetic disease-causing mutations. However, in vivo gene editing using CRISPR/Cas9 remains a major challenge currently limiting its therapeutic application for disease correction. In the present study, we developed novel Cas9/gRNA nanocomplexes that lead to efficient in vivo gene targeting of neurons in the brain. We demonstrate the in vivo efficacy of Cas9-nanocomplexes as therapeutic agents for Alzheimer’s disease (AD) by targeting the BACE1 gene. Remarkably, in vivo BACE1 targeting by using Cas9-nanocomplexes results in decreased Aβ42 production and improvement of cognitive decline in an AD mouse model. These results suggest that Cas9-nanocomplexes represent an effective in vivo gene editing platform in the brain, and that this strategy may be applicable to the treatment of a broad range of neurological diseases.
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| Overall design |
HEK 293T cell was used for human control and CRISPR/Cas9 nanocomplex (Nano) treated samples. Mouse brain was used for control and CRISPR/Cas9 nanocomplex (Nano) treated samples. For human samples, PCR amplicons of 4 target sites were pooled and sequenced (total 2 samples). For mouse samples, PCR amplicons of 4 target sites were sequenced separately (total 8 samples).
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| Contributor(s) |
Park H, Oh J, Park J, Chang Y, Baek S, Kim H, Chio H, Yoo J, Lee M, Lengner CJ, Kim J |
| Citation missing |
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| |
| Submission date |
Mar 10, 2017 |
| Last update date |
Mar 10, 2020 |
| Contact name |
Jihwan Park |
| E-mail(s) |
jihwan.park724@gmail.com
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| Organization name |
GWANGJU INSTITUTE OF SCIENCE /TECHNOLOGY
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| Street address |
123 Cheomdangwagi-ro
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| City |
Bukgu |
| State/province |
Gwangju |
| ZIP/Postal code |
61005 |
| Country |
South Korea |
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| Platforms (2) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA378729 |
| SRA |
SRP101710 |
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