Programmable C:G to G:C genome editing with CRISPR-Cas9-directed base excision repair proteins

Liwei Chen, Jung Eun Park, Peter Paa, Priscilla D. Rajakumar, Hong-Ting Prekop, Yi Ting Chew, Swathi N. Manivannan and Wei Leong Chew ()
Additional contact information
Liwei Chen: Genome Institute of Singapore, Agency for Science, Technology and Research
Jung Eun Park: Genome Institute of Singapore, Agency for Science, Technology and Research
Peter Paa: Genome Institute of Singapore, Agency for Science, Technology and Research
Priscilla D. Rajakumar: Genome Institute of Singapore, Agency for Science, Technology and Research
Hong-Ting Prekop: Genome Institute of Singapore, Agency for Science, Technology and Research
Yi Ting Chew: Genome Institute of Singapore, Agency for Science, Technology and Research
Swathi N. Manivannan: Genome Institute of Singapore, Agency for Science, Technology and Research
Wei Leong Chew: Genome Institute of Singapore, Agency for Science, Technology and Research

Nature Communications, 2021, vol. 12, issue 1, 1-7

Abstract: Abstract Many genetic diseases are caused by single-nucleotide polymorphisms. Base editors can correct these mutations at single-nucleotide resolution, but until recently, only allowed for transition edits, addressing four out of twelve possible DNA base substitutions. Here, we develop a class of C:G to G:C Base Editors to create single-base genomic transversions in human cells. Our C:G to G:C Base Editors consist of a nickase-Cas9 fused to a cytidine deaminase and base excision repair proteins. Characterization of >30 base editor candidates reveal that they predominantly perform C:G to G:C editing (up to 90% purity), with rAPOBEC-nCas9-rXRCC1 being the most efficient (mean 15.4% and up to 37% without selection). C:G to G:C Base Editors target cytidine in WCW, ACC or GCT sequence contexts and within a precise three-nucleotide window of the target protospacer. We further target genes linked to dyslipidemia, hypertrophic cardiomyopathy, and deafness, showing the therapeutic potential of these base editors in interrogating and correcting human genetic diseases.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-21559-9 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:12:y:2021:i:1:d:10.1038_s41467-021-21559-9

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

DOI: 10.1038/s41467-021-21559-9

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 ().