Journal
NATURE BIOTECHNOLOGY
Volume 37, Issue 6, Pages 626-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41587-019-0134-y
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Funding
- US NIH [DP2 EB018658, U01 AI142756, RM1 HG009490, R01 EB022376, R35 GM118062, K99 GM118909, R00 GM118909]
- St. Jude Research Consortium
- Ono Pharma Foundation
- DARPA [HR0011-17-2-0049]
- HHMI
- Harvard Chemical Biology Program NIH Training Grant [T32 GM095450]
- NSF graduate fellowship
- Innovative Genomic Institute Entrepreneurial Fellowship Program
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Base editing requires that the target sequence satisfy the protospacer adjacent motif requirement of the Cas9 domain and that the target nucleotide be located within the editing window of the base editor. To increase the targeting scope of base editors, we engineered six optimized adenine base editors (ABEmax variants) that use SpCas9 variants compatible with non-NGG protospacer adjacent motifs. To increase the range of target bases that can be modified within the protospacer, we use circularly permuted Cas9 variants to produce four cytosine and four adenine base editors with an editing window expanded from similar to 4-5 nucleotides to up to similar to 8-9 nucleotides and reduced byproduct formation. This set of base editors improves the targeting scope of cytosine and adenine base editing.
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