In vivo genome editing using Staphylococcus aureus Cas9

F. Ann Ran, Le Cong, Winston X. Yan, David A. Scott, Jonathan S. Gootenberg, Andrea J. Kriz, Bernd Zetsche, Ophir Shalem, Xuebing Wu, Kira S. Makarova, Eugene V. Koonin, Phillip A. Sharp and Feng Zhang ()
Additional contact information
F. Ann Ran: Broad Institute of MIT and Harvard
Le Cong: Broad Institute of MIT and Harvard
Winston X. Yan: Broad Institute of MIT and Harvard
David A. Scott: Broad Institute of MIT and Harvard
Jonathan S. Gootenberg: Broad Institute of MIT and Harvard
Andrea J. Kriz: Massachusetts Institute of Technology
Bernd Zetsche: Broad Institute of MIT and Harvard
Ophir Shalem: Broad Institute of MIT and Harvard
Xuebing Wu: David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
Kira S. Makarova: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health
Eugene V. Koonin: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health
Phillip A. Sharp: Massachusetts Institute of Technology
Feng Zhang: Broad Institute of MIT and Harvard

Nature, 2015, vol. 520, issue 7546, 186-191

Abstract: 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.

Date: 2015
References: Add references at CitEc
Citations: View citations in EconPapers (24)

Downloads: (external link)
https://www.nature.com/articles/nature14299 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:520:y:2015:i:7546:d:10.1038_nature14299

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature14299

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().