Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype

被引：700

作者：

Yin, Hao ^{[1
]}

Xue, Wen ^{[1
]}

Chen, Sidi ^{[1
]}

Bogorad, Roman L. ^{[1
]}

Benedetti, Eric ^{[2
]}

Grompe, Markus ^{[2
]}

Koteliansky, Victor ^{[3
]}

Sharp, Phillip A. ^{[1
]}

Jacks, Tyler ^{[1
,4
,5
]}

Anderson, Daniel G. ^{[1
,6
,7
,8
]}

机构：

[1] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA

[2] Oregon Hlth & Sci Univ, Dept Pediat, Oregon Stem Cell Ctr, Portland, OR 97201 USA

[3] Skolkovo Inst Sci & Technol, Skolkovo, Russia

[4] MIT, Dept Biol, Cambridge, MA 02139 USA

[5] MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA

[6] MIT, Dept Chem Engn, Cambridge, MA 02139 USA

[7] Harvard MIT, Div Hlth Sci & Technol, Cambridge, MA USA

[8] MIT, Inst Med Engn & Sci, Cambridge, MA 02139 USA

来源：

NATURE BIOTECHNOLOGY | 2014年 / 32卷 / 06期

基金：

美国国家卫生研究院;

关键词：

MOUSE MODEL; HUMAN-CELLS; IN-VIVO; SPECIFICITY; NUCLEASES; REPAIR; GENE; DNA;

D O I：

10.1038/nbt.2884

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

We demonstrate CRISPR-Cas9-mediated correction of a Fah mutation in hepatocytes in a mouse model of the human disease hereditary tyrosinemia. Delivery of components of the CRISPR-Cas9 system by hydrodynamic injection resulted in initial expression of the wild-type Fah protein in similar to 1/250 liver cells. Expansion of Fah-positive hepatocytes rescued the body weight loss phenotype. Our study indicates that CRISPR-Cas9-mediated genome editing is possible in adult animals and has potential for correction of human genetic diseases.

引用

页码：551 / 553

页数：3

共 15 条

[11] SNP Calling, Genotype Calling, and Sample Allele Frequency Estimation from New-Generation Sequencing Data [J].

Nielsen, Rasmus ;

Korneliussen, Thorfinn ;

Albrechtsen, Anders ;

Li, Yingrui ;

Wang, Jun .

PLOS ONE, 2012, 7 (07)

[12] Adeno-Associated Virus Gene Repair Corrects a Mouse Model of Hereditary Tyrosinemia In Vivo [J].

Paulk, Nicole K. ;

Wursthorn, Karsten ;

Wang, Zhongya ;

Finegold, Milton J. ;

Kay, Mark A. ;

Grompe, Markus .

HEPATOLOGY, 2010, 51 (04) :1200-1208

[13] Double Nicking by RNA-Guided CRISPR Cas9 for Enhanced Genome Editing Specificity [J].

Ran, F. Ann ;

Hsu, Patrick D. ;

Lin, Chie-Yu ;

Gootenberg, Jonathan S. ;

Konermann, Silvana ;

Trevino, Alexandro E. ;

Scott, David A. ;

Inoue, Azusa ;

Matoba, Shogo ;

Zhang, Yi ;

Zhang, Feng .

CELL, 2013, 154 (06) :1380-1389

[14] Functional Repair of CFTR by CRISPR/Cas9 in Intestinal Stem Cell Organoids of Cystic Fibrosis Patients [J].

Schwank, Gerald ;

Koo, Bon-Kyoung ;

Sasselli, Valentina ;

Dekkers, Johanna F. ;

Heo, Inha ;

Demircan, Turan ;

Sasaki, Nobuo ;

Boymans, Sander ;

Cuppen, Edwin ;

van der Ent, Cornelis K. ;

Nieuwenhuis, Edward E. S. ;

Beekman, Jeffrey M. ;

Clevers, Hans .

CELL STEM CELL, 2013, 13 (06) :653-658

[15] Correction of a Genetic Disease in Mouse via Use of CRISPR-Cas9 [J].

Wu, Yuxuan ;

Liang, Dan ;

Wang, Yinghua ;

Bai, Meizhu ;

Tang, Wei ;

Bao, Shiming ;

Yan, Zhiqiang ;

Li, Dangsheng ;

Li, Jinsong .

CELL STEM CELL, 2013, 13 (06) :659-662

← 1 2 →