Correction of a genetic disease in mouse via use of CRISPR-Cas9

The CRISPR-Cas9 system has been employed to generate mutant alleles in a range of different organisms. However, so far there have not been reports of use of this system for efficient correction of a genetic disease. Here we show that mice with a dominant mutation in Crygc gene that causes cataracts...

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Bibliographic Details
Published in:Cell stem cell Vol. 13; no. 6; p. 659
Main Authors: Wu, Yuxuan, Liang, Dan, Wang, Yinghua, Bai, Meizhu, Tang, Wei, Bao, Shiming, Yan, Zhiqiang, Li, Dangsheng, Li, Jinsong
Format: Journal Article
Language:English
Published: United States 05.12.2013
Subjects:
Animals
Base Sequence
Cataract - genetics
Cataract - therapy
Clustered Regularly Interspaced Short Palindromic Repeats - genetics
CRISPR-Associated Proteins - metabolism
Disease Models, Animal
gamma-Crystallins - genetics
gamma-Crystallins - therapeutic use
Genetic Therapy
Mice
Molecular Sequence Data
RNA, Messenger - genetics
RNA, Messenger - metabolism
ISSN:1875-9777, 1875-9777
Online Access:Get more information
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Summary:The CRISPR-Cas9 system has been employed to generate mutant alleles in a range of different organisms. However, so far there have not been reports of use of this system for efficient correction of a genetic disease. Here we show that mice with a dominant mutation in Crygc gene that causes cataracts could be rescued by coinjection into zygotes of Cas9 mRNA and a single-guide RNA (sgRNA) targeting the mutant allele. Correction occurred via homology-directed repair (HDR) based on an exogenously supplied oligonucleotide or the endogenous WT allele, with only rare evidence of off-target modifications. The resulting mice were fertile and able to transmit the corrected allele to their progeny. Thus, our study provides proof of principle for use of the CRISPR-Cas9 system to correct genetic disease.
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ISSN:1875-9777
1875-9777
DOI:10.1016/j.stem.2013.10.016