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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| Veröffentlicht in: | Nature biotechnology Jg. 38; H. 7; S. 865 - 869 |
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| Sprache: | Englisch |
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United States
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01.07.2020
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| ISSN: | 1087-0156, 1546-1696, 1546-1696 |
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| Abstract | 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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| AbstractList | 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.Base editors that modify both adenosine and cytosine broaden the potential applications of base editing. 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.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. 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. |
| Author | Yamamoto, Shogo Kondo, Akihiko Nishimasu, Hiroshi Mori, Hideto Nureki, Osamu Tatsuno, Kenji Seki, Motoaki Tanaka, Mamoru Masuyama, Nanami Arakawa, Kazuharu Ishiguro, Soh Ueda, Hiroki Nishida, Keiji Tomita, Masaru Sakata, Rina C Aburatani, Hiroyuki Yachie, Nozomu |
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| Snippet | We describe base editors that combine both cytosine and adenine base-editing functions. A codon-optimized fusion of the cytosine deaminase PmCDA1, the... |
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| SubjectTerms | 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 |
| Title | Base editors for simultaneous introduction of C-to-T and A-to-G mutations |
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