Compact zinc finger architecture utilizing toxin-derived cytidine deaminases for highly efficient base editing in human cells

Friedrich Fauser, Bhakti N. Kadam, Sebastian Arangundy-Franklin, Jessica E. Davis, Vishvesha Vaidya, Nicola J. Schmidt, Garrett Lew, Danny F. Xia, Rakshaa Mureli, Colman Ng, Yuanyue Zhou, Nicholas A. Scarlott, Jason Eshleman, Yuri R. Bendaña, David A. Shivak, Andreas Reik, Patrick Li, Gregory D. Davis and Jeffrey C. Miller ()
Additional contact information
Friedrich Fauser: Sangamo Therapeutics, Inc.
Bhakti N. Kadam: Sangamo Therapeutics, Inc.
Sebastian Arangundy-Franklin: Sangamo Therapeutics, Inc.
Jessica E. Davis: Sangamo Therapeutics, Inc.
Vishvesha Vaidya: Sangamo Therapeutics, Inc.
Nicola J. Schmidt: Sangamo Therapeutics, Inc.
Garrett Lew: Sangamo Therapeutics, Inc.
Danny F. Xia: Sangamo Therapeutics, Inc.
Rakshaa Mureli: Sangamo Therapeutics, Inc.
Colman Ng: Sangamo Therapeutics, Inc.
Yuanyue Zhou: Sangamo Therapeutics, Inc.
Nicholas A. Scarlott: Sangamo Therapeutics, Inc.
Jason Eshleman: Sangamo Therapeutics, Inc.
Yuri R. Bendaña: Sangamo Therapeutics, Inc.
David A. Shivak: Sangamo Therapeutics, Inc.
Andreas Reik: Sangamo Therapeutics, Inc.
Patrick Li: Sangamo Therapeutics, Inc.
Gregory D. Davis: Sangamo Therapeutics, Inc.
Jeffrey C. Miller: Sangamo Therapeutics, Inc.

Nature Communications, 2024, vol. 15, issue 1, 1-11

Abstract: Abstract Nucleobase editors represent an emerging technology that enables precise single-base edits to the genomes of eukaryotic cells. Most nucleobase editors use deaminase domains that act upon single-stranded DNA and require RNA-guided proteins such as Cas9 to unwind the DNA prior to editing. However, the most recent class of base editors utilizes a deaminase domain, DddAtox, that can act upon double-stranded DNA. Here, we target DddAtox fragments and a FokI-based nickase to the human CIITA gene by fusing these domains to arrays of engineered zinc fingers (ZFs). We also identify a broad variety of Toxin-Derived Deaminases (TDDs) orthologous to DddAtox that allow us to fine-tune properties such as targeting density and specificity. TDD-derived ZF base editors enable up to 73% base editing in T cells with good cell viability and favorable specificity.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-45100-w 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:15:y:2024:i:1:d:10.1038_s41467-024-45100-w

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

DOI: 10.1038/s41467-024-45100-w

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 ().