Journal
CELL RESEARCH
Volume 28, Issue 8, Pages 855-861Publisher
INST BIOCHEMISTRY & CELL BIOLOGY
DOI: 10.1038/s41422-018-0052-4
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Funding
- National Key RD Program [2017YFC1001903, 2016YFC0905901]
- National Science Foundation of China [31471400, 39870046, 81270605, 30971066, 81470324]
- Major technological innovation plan of hospital [SWH2016ZDCX1003, SWH2016ZDCX1010]
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Base editor (BE), containing a cytidine deaminase and catalytically defective Cas9, has been widely used to perform base editing. However, the narrow editing window of BE limits its utility. Here, we developed a new editing technology named as base editor for programming larger C to U (T) scope (BE-PLUS) by fusing 10 copies of GCN4 peptide to nCas9(D10A) for recruiting scFv-APOBEC-UGI-GB1 to the target sites. The new system achieves base editing with a broadened window, resulting in an increased genome-targeting scope. Interestingly, the new system yielded much fewer unwanted indels and non-C-to-T conversions. We also demonstrated its potential use in gene disruption across the whole genome through induction of stop codons (iSTOP). Taken together, the BE-PLUS system offers a new editing tool with increased editing window and enhanced fidelity.
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