In vivo neuronal gene editing via CRISPR–Cas9 amphiphilic nanocomplexes alleviates deficits in mouse models of Alzheimer’s disease

Hanseul Park; Jungju Oh; Gayong Shim; Byounggook Cho; Yujung Chang; Siyoung Kim; Soonbong Baek; Hongwon Kim; Jeain Shin; Hwan Choi; Junsang Yoo; Junyeop Kim; Won Jun; Minhyung Lee; Christopher J. Lengner; Yu Kyoung Oh; Jongpil Kim

doi:10.1038/s41593-019-0352-0

In vivo neuronal gene editing via CRISPR–Cas9 amphiphilic nanocomplexes alleviates deficits in mouse models of Alzheimer’s disease

Hanseul Park
, Jungju Oh
, Gayong Shim
, Byounggook Cho
, Yujung Chang
, Siyoung Kim
, Soonbong Baek
, Hongwon Kim
, Jeain Shin
, Hwan Choi
, Junsang Yoo
, Junyeop Kim
, Won Jun
, Minhyung Lee
, Christopher J. Lengner
, Yu Kyoung Oh
, Jongpil Kim

Department of Chemistry

Dongguk University
Hanyang University
Seoul National University
Dankook University
University of Pennsylvania

Research output: Contribution to journal › Article › peer-review

247 Scopus citations

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.

Original language	English
Pages (from-to)	524-528
Number of pages	5
Journal	Nature Neuroscience
Volume	22
Issue number	4
DOIs	https://doi.org/10.1038/s41593-019-0352-0
State	Published - 1 Apr 2019

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Park, H., Oh, J., Shim, G., Cho, B., Chang, Y., Kim, S., Baek, S., Kim, H., Shin, J., Choi, H., Yoo, J., Kim, J., Jun, W., Lee, M., Lengner, C. J., Oh, Y. K., & Kim, J. (2019). In vivo neuronal gene editing via CRISPR–Cas9 amphiphilic nanocomplexes alleviates deficits in mouse models of Alzheimer’s disease. Nature Neuroscience, 22(4), 524-528. https://doi.org/10.1038/s41593-019-0352-0

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title = "In vivo neuronal gene editing via CRISPR–Cas9 amphiphilic nanocomplexes alleviates deficits in mouse models of Alzheimer{\textquoteright}s disease",

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{\textquoteright}s disease. These results broaden the potential application of CRISPR–Cas9 systems to neurodegenerative diseases.",

author = "Hanseul Park and Jungju Oh and Gayong Shim and Byounggook Cho and Yujung Chang and Siyoung Kim and Soonbong Baek and Hongwon Kim and Jeain Shin and Hwan Choi and Junsang Yoo and Junyeop Kim and Won Jun and Minhyung Lee and Lengner, \{Christopher J.\} and Oh, \{Yu Kyoung\} and Jongpil Kim",

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2019",

month = apr,

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doi = "10.1038/s41593-019-0352-0",

language = "English",

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Park, H, Oh, J, Shim, G, Cho, B, Chang, Y, Kim, S, Baek, S, Kim, H, Shin, J, Choi, H, Yoo, J, Kim, J, Jun, W, Lee, M, Lengner, CJ, Oh, YK & Kim, J 2019, 'In vivo neuronal gene editing via CRISPR–Cas9 amphiphilic nanocomplexes alleviates deficits in mouse models of Alzheimer’s disease', Nature Neuroscience, vol. 22, no. 4, pp. 524-528. https://doi.org/10.1038/s41593-019-0352-0

TY - JOUR

T1 - In vivo neuronal gene editing via CRISPR–Cas9 amphiphilic nanocomplexes alleviates deficits in mouse models of Alzheimer’s disease

AU - Park, Hanseul

AU - Oh, Jungju

AU - Shim, Gayong

AU - Cho, Byounggook

AU - Chang, Yujung

AU - Kim, Siyoung

AU - Baek, Soonbong

AU - Kim, Hongwon

AU - Shin, Jeain

AU - Choi, Hwan

AU - Yoo, Junsang

AU - Kim, Junyeop

AU - Jun, Won

AU - Lee, Minhyung

AU - Lengner, Christopher J.

AU - Oh, Yu Kyoung

AU - Kim, Jongpil

PY - 2019/4/1

Y1 - 2019/4/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85062819266

U2 - 10.1038/s41593-019-0352-0

DO - 10.1038/s41593-019-0352-0

M3 - Article

C2 - 30858603

AN - SCOPUS:85062819266

SN - 1097-6256

VL - 22

SP - 524

EP - 528

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 4

ER -

In vivo neuronal gene editing via CRISPR–Cas9 amphiphilic nanocomplexes alleviates deficits in mouse models of Alzheimer’s disease

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