Base editors for simultaneous introduction of C-to-T and A-to-G mutations

We describe base editors that combine both cytosine and adenine base-editing functions. A codon-optimized fusion of the cytosine deaminase PmCDA1, the adenosine deaminase TadA and a Cas9 nickase (Target-ACEmax) showed a high median simultaneous C-to-T and A-to-G editing activity at 47 genomic target...

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Bibliographic Details
Published in:Nature biotechnology Vol. 38; no. 7; pp. 865 - 869
Main Authors: Sakata, Rina C, Ishiguro, Soh, Mori, Hideto, Tanaka, Mamoru, Tatsuno, Kenji, Ueda, Hiroki, Yamamoto, Shogo, Seki, Motoaki, Masuyama, Nanami, Nishida, Keiji, Nishimasu, Hiroshi, Arakawa, Kazuharu, Kondo, Akihiko, Nureki, Osamu, Tomita, Masaru, Aburatani, Hiroyuki, Yachie, Nozomu
Format: Journal Article
Language:English
Published: United States Nature Publishing Group 01.07.2020
Subjects:
Adenine
Adenine - metabolism
Adenosine
Adenosine deaminase
Adenosine Deaminase - genetics
CRISPR-Associated Protein 9 - genetics
CRISPR-Cas Systems - genetics
Cytosine
Cytosine - metabolism
Cytosine deaminase
Deoxyribonuclease I - genetics
Deoxyribonucleic acid
DNA
DNA - genetics
Editing
Gene Editing
Genome, Human - genetics
Glycoproteins - genetics
Guanine - metabolism
HEK293 Cells
Humans
Mutation
Mutation - genetics
Nuclear Proteins - genetics
Ribonucleic acid
RNA
RNA - genetics
ISSN:1087-0156, 1546-1696, 1546-1696
Online Access:Get full text
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Summary:We describe base editors that combine both cytosine and adenine base-editing functions. A codon-optimized fusion of the cytosine deaminase PmCDA1, the adenosine deaminase TadA and a Cas9 nickase (Target-ACEmax) showed a high median simultaneous C-to-T and A-to-G editing activity at 47 genomic targets. On-target as well as DNA and RNA off-target activities of Target-ACEmax were similar to those of existing single-function base editors.
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ISSN:1087-0156
1546-1696
1546-1696
DOI:10.1038/s41587-020-0509-0