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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Podrobná bibliografia
Vydané v:	Nature biotechnology Ročník 38; číslo 7; s. 865 - 869
Hlavní autori:	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
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States Nature Publishing Group 01.07.2020
Predmet:	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
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Popis
Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1087-0156 1546-1696 1546-1696
DOI:	10.1038/s41587-020-0509-0