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

[1] Point mutations in the murine fumarylacetoacetate hydrolase gene: Animal models for the human genetic disorder hereditary tyrosinemia type 1 [J].

Aponte, JL ;

Sega, GA ;

Hauser, LJ ;

Dhar, MS ;

Withrow, CM ;

Carpenter, DA ;

Rinchik, EM ;

Culiat, CT ;

Johnson, DK .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (02) :641-645

[2] Robust expansion of human hepatocytes in Fah-/-/Rag2-/-/Il2rg-/- mice [J].

Azuma, Hisaya ;

Paulk, Nicole ;

Ranade, Aarati ;

Dorrell, Craig ;

Al-Dhalimy, Muhsen ;

Ellis, Ewa ;

Strom, Stephen ;

Kay, Mark A. ;

Finegold, Milton ;

Grompe, Markus .

NATURE BIOTECHNOLOGY, 2007, 25 (08) :903-910

[3] Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease [J].

Cho, Seung Woo ;

Kim, Sojung ;

Kim, Jong Min ;

Kim, Jin-Soo .

NATURE BIOTECHNOLOGY, 2013, 31 (03) :230-232

[4] Multiplex Genome Engineering Using CRISPR/Cas Systems [J].

Cong, Le ;

Ran, F. Ann ;

Cox, David ;

Lin, Shuailiang ;

Barretto, Robert ;

Habib, Naomi ;

Hsu, Patrick D. ;

Wu, Xuebing ;

Jiang, Wenyan ;

Marraffini, Luciano A. ;

Zhang, Feng .

SCIENCE, 2013, 339 (6121) :819-823

[5] High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells [J].

Fu, Yanfang ;

Foden, Jennifer A. ;

Khayter, Cyd ;

Maeder, Morgan L. ;

Reyon, Deepak ;

Joung, J. Keith ;

Sander, Jeffry D. .

NATURE BIOTECHNOLOGY, 2013, 31 (09) :822-+

[6] DNA targeting specificity of RNA-guided Cas9 nucleases [J].

Hsu, Patrick D. ;

Scott, David A. ;

Weinstein, Joshua A. ;

Ran, F. Ann ;

Konermann, Silvana ;

Agarwala, Vineeta ;

Li, Yinqing ;

Fine, Eli J. ;

Wu, Xuebing ;

Shalem, Ophir ;

Cradick, Thomas J. ;

Marraffini, Luciano A. ;

Bao, Gang ;

Zhang, Feng .

NATURE BIOTECHNOLOGY, 2013, 31 (09) :827-+

[7]

Kanasty R, 2013, NAT MATER, V12, P967, DOI [10.1038/NMAT3765, 10.1038/nmat3765]

[8] In vivo genome editing restores haemostasis in a mouse model of haemophilia [J].

Li, Hojun ;

Haurigot, Virginia ;

Doyon, Yannick ;

Li, Tianjian ;

Wong, Sunnie Y. ;

Bhagwat, Anand S. ;

Malani, Nirav ;

Anguela, Xavier M. ;

Sharma, Rajiv ;

Ivanciu, Lacramiora ;

Murphy, Samuel L. ;

Finn, Jonathan D. ;

Khazi, Fayaz R. ;

Zhou, Shangzhen ;

Paschon, David E. ;

Rebar, Edward J. ;

Bushman, Frederic D. ;

Gregory, Philip D. ;

Holmes, Michael C. ;

High, Katherine A. .

NATURE, 2011, 475 (7355) :217-U128

[9] Hydrodynamics-based transfection in animals by systemic administration of plasmid DNA [J].

Liu, F ;

Song, YK ;

Liu, D .

GENE THERAPY, 1999, 6 (07) :1258-1266

[10] RNA-Guided Human Genome Engineering via Cas9 [J].

Mali, Prashant ;

Yang, Luhan ;

Esvelt, Kevin M. ;

Aach, John ;

Guell, Marc ;

DiCarlo, James E. ;

Norville, Julie E. ;

Church, George M. .

SCIENCE, 2013, 339 (6121) :823-826

← 1 2 →