Orthogonal Cas9–Cas9 chimeras provide a versatile platform for genome editing

Mehmet Fatih Bolukbasi, Pengpeng Liu, Kevin Luk, Samantha F. Kwok, Ankit Gupta, Nadia Amrani, Erik J. Sontheimer, Lihua Julie Zhu and Scot A. Wolfe ()
Additional contact information
Mehmet Fatih Bolukbasi: University of Massachusetts Medical School
Pengpeng Liu: University of Massachusetts Medical School
Kevin Luk: University of Massachusetts Medical School
Samantha F. Kwok: University of Massachusetts Medical School
Ankit Gupta: University of Massachusetts Medical School
Nadia Amrani: University of Massachusetts Medical School
Erik J. Sontheimer: University of Massachusetts Medical School
Lihua Julie Zhu: University of Massachusetts Medical School
Scot A. Wolfe: University of Massachusetts Medical School

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract The development of robust, versatile and accurate toolsets is critical to facilitate therapeutic genome editing applications. Here we establish RNA-programmable Cas9-Cas9 chimeras, in single- and dual-nuclease formats, as versatile genome engineering systems. In both of these formats, Cas9-Cas9 fusions display an expanded targeting repertoire and achieve highly specific genome editing. Dual-nuclease Cas9-Cas9 chimeras have distinct advantages over monomeric Cas9s including higher target site activity and the generation of predictable precise deletion products between their target sites. At a therapeutically relevant site within the BCL11A erythroid enhancer, Cas9-Cas9 nucleases produced precise deletions that comprised up to 97% of all sequence alterations. Thus Cas9-Cas9 chimeras represent an important tool that could be particularly valuable for therapeutic genome editing applications where a precise cleavage position and defined sequence end products are desirable.

Date: 2018
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-018-07310-x Abstract (text/html)

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:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-07310-x

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

DOI: 10.1038/s41467-018-07310-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

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