胞嘧啶
清脆的
Cas9
核苷酸
范围(计算机科学)
基础(拓扑)
计算生物学
碱基对
基因组编辑
DNA
生物
遗传学
计算机科学
程序设计语言
基因
数学
数学分析
作者
Tony P. Huang,Kevin T. Zhao,Shannon M. Miller,Nicole M. Gaudelli,Benjamin L. Oakes,Christof Fellmann,David F. Savage,David R. Liu
标识
DOI:10.1038/s41587-019-0134-y
摘要
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 ~4-5 nucleotides to up 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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