Journal Article

PUBDB-2023-03453

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Improved cytosine base editors generated from TadA variants

Lam, D. K. ; Feliciano, P. R. ; Arif, A. ; Bohnuud, T. ; Fernandez, T. P. ; Gehrke, J. M. ; Grayson, P. ; Lee, K. D. ; Ortega, M. A. ; Sawyer, C. ; Schwaegerle, N. D. ; Peraro, L. ; Young, L. ; Lee, S.-J. ; Ciaramella, G. ; Gaudelli, N. M. (Corresponding author)

2023
Springer Nature New York, NY

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Please use a persistent id in citations: doi:10.1038/s41587-022-01611-9  doi:10.3204/PUBDB-2023-03453

Abstract: Cytosine base editors (CBEs) enable programmable genomic C·G-to-T·A transition mutations and typically comprise a modified CRISPR–Cas enzyme, a naturally occurring cytidine deaminase, and an inhibitor of uracil repair. Previous studies have shown that CBEs utilizing naturally occurring cytidine deaminases may cause unguided, genome-wide cytosine deamination. While improved CBEs that decrease stochastic genome-wide off-targets have subsequently been reported, these editors can suffer from suboptimal on-target performance. Here, we report the generation and characterization of CBEs that use engineered variants of TadA (CBE-T) that enable high on-target C·G to T·A across a sequence-diverse set of genomic loci, demonstrate robust activity in primary cells and cause no detectable elevation in genome-wide mutation. Additionally, we report cytosine and adenine base editors (CABEs) catalyzing both A-to-I and C-to-U editing (CABE-Ts). Together with ABEs, CBE-Ts and CABE-Ts enable the programmable installation of all transition mutations using laboratory-evolved TadA variants with improved properties relative to previously reported CBEs.

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Contributing Institute(s):

1. EMBL-User (EMBL-User)

Research Program(s):

1. 6G3 - PETRA III (DESY) (POF4-6G3) (POF4-6G3)

Experiment(s):

1. PETRA Beamline P13 (PETRA III)

Appears in the scientific report 2023

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; DEAL Nature ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 40 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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