HMGN1 enhances CRISPR-directed dual-function A-to-G and C-to-G base editing

Author:

Yang Chao,Ma Zhenzhen,Wang Keshan,Dong Xingxiao,Huang Meiyu,Li Yaqiu,Zhu Xiagu,Li JuORCID,Cheng Zhihui,Bi ChanghaoORCID,Zhang XueliORCID

Abstract

AbstractC-to-G base editors have been successfully constructed recently, but limited work has been done on concurrent C-to-G and A-to-G base editing. In addition, there is also limited data on how chromatin-associated factors affect the base editing. Here, we test a series of chromatin-associated factors, and chromosomal protein HMGN1 was found to enhance the efficiency of both C-to-G and A-to-G base editing. By fusing HMGN1, GBE and ABE to Cas9, we develop a CRISPR-based dual-function A-to-G and C-to-G base editor (GGBE) which is capable of converting simultaneous A and C to G conversion with substantial editing efficiency. Accordingly, the HMGN1 role shown in this work and the resulting GGBE tool further broaden the genome manipulation capacity of CRISPR-directed base editors.

Funder

National Natural Science Foundation of China

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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