title: Correction of a genetic disease in mouse via use of CRISPR-Cas9.
abstract: 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.
authors: Group of Epigenetic Reprogramming, State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
authors: Yuxuan
authors: Y
authors: Wu
authors: Dan
authors: D
authors: Liang
authors: Yinghua
authors: Y
authors: Wang
authors: Meizhu
authors: M
authors: Bai
authors: Wei
authors: W
authors: Tang
authors: Shiming
authors: S
authors: Bao
authors: Zhiqiang
authors: Z
authors: Yan
authors: Dangsheng
authors: D
authors: Li
authors: Jinsong
authors: J
authors: Li
mesh_terms: D000818:Animals; D001483:Base Sequence; D064130:CRISPR-Associated Proteins / Q000378:metabolism*; D002386:Cataract / Q000235:genetics* / Q000628:therapy*; D064112:Clustered Regularly Interspaced Short Palindromic Repeats / Q000235:genetics*; D004195:Disease Models, Animal; D015316:Genetic Therapy; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D038222:gamma-Crystallins / Q000235:genetics / Q000627:therapeutic use
chemical_list: D064130:CRISPR-Associated Proteins; D012333:RNA, Messenger; D038222:gamma-Crystallins