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In vivo genome editing using Staphylococcus aureus Cas9.

作者信息

Ran F Ann, Cong Le, Yan Winston X, Scott David A, Gootenberg Jonathan S, Kriz Andrea J, Zetsche Bernd, Shalem Ophir, Wu Xuebing, Makarova Kira S, Koonin Eugene V, Sharp Phillip A, Zhang Feng

机构信息

1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Society of Fellows, Harvard University, Cambridge, Massachusetts 02138, USA.

1] Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA [2] Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

出版信息

Nature. 2015 Apr 9;520(7546):186-91. doi: 10.1038/nature14299. Epub 2015 Apr 1.

DOI:10.1038/nature14299
PMID:25830891
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4393360/
Abstract

The RNA-guided endonuclease Cas9 has emerged as a versatile genome-editing platform. However, the size of the commonly used Cas9 from Streptococcus pyogenes (SpCas9) limits its utility for basic research and therapeutic applications that use the highly versatile adeno-associated virus (AAV) delivery vehicle. Here, we characterize six smaller Cas9 orthologues and show that Cas9 from Staphylococcus aureus (SaCas9) can edit the genome with efficiencies similar to those of SpCas9, while being more than 1 kilobase shorter. We packaged SaCas9 and its single guide RNA expression cassette into a single AAV vector and targeted the cholesterol regulatory gene Pcsk9 in the mouse liver. Within one week of injection, we observed >40% gene modification, accompanied by significant reductions in serum Pcsk9 and total cholesterol levels. We further assess the genome-wide targeting specificity of SaCas9 and SpCas9 using BLESS, and demonstrate that SaCas9-mediated in vivo genome editing has the potential to be efficient and specific.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/bee84253ae47/nihms661947f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/01948cc4a3bc/nihms661947f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/d2b9e645bcfd/nihms661947f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/d26aac13e830/nihms661947f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/115bc7cba794/nihms661947f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/ca1d12c1d326/nihms661947f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/9e05fe7442e1/nihms661947f11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/1e6040c85b57/nihms661947f12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/6aeebef03162/nihms661947f13.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/380167527034/nihms661947f14.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/c53b02de7743/nihms661947f15.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/83c31ae763ed/nihms661947f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/8397e09c797e/nihms661947f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/13f827ac702d/nihms661947f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/1a17ece650fb/nihms661947f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/bee84253ae47/nihms661947f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/01948cc4a3bc/nihms661947f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/d2b9e645bcfd/nihms661947f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/d26aac13e830/nihms661947f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/115bc7cba794/nihms661947f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/ca1d12c1d326/nihms661947f10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/9e05fe7442e1/nihms661947f11.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/1e6040c85b57/nihms661947f12.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/6aeebef03162/nihms661947f13.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/380167527034/nihms661947f14.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/c53b02de7743/nihms661947f15.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/83c31ae763ed/nihms661947f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/8397e09c797e/nihms661947f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/13f827ac702d/nihms661947f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/1a17ece650fb/nihms661947f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8eb2/4393360/bee84253ae47/nihms661947f5.jpg

相似文献

[1]
In vivo genome editing using Staphylococcus aureus Cas9.

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[4]
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[9]
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[10]
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本文引用的文献

[1]
GUIDE-seq enables genome-wide profiling of off-target cleavage by CRISPR-Cas nucleases.

Nat Biotechnol. 2015-2

[2]
Genome-wide detection of DNA double-stranded breaks induced by engineered nucleases.

Nat Biotechnol. 2015-2

[3]
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Mol Cell. 2014-10-16

[4]
In vivo interrogation of gene function in the mammalian brain using CRISPR-Cas9.

Nat Biotechnol. 2015-1

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Biotechnol J. 2014-11

[6]
Development and applications of CRISPR-Cas9 for genome engineering.

Cell. 2014-6-5

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Nucleic Acids Res. 2014-6

[8]
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Nat Biotechnol. 2014-5-18

[9]
Genome-wide binding of the CRISPR endonuclease Cas9 in mammalian cells.

Nat Biotechnol. 2014-4-20

[10]
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Nucleic Acids Res. 2014-6

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