BE-PLUS: a new base editing tool with broadened editing window and enhanced fidelity

Cell Res. 2018 Aug;28(8):855-861. doi: 10.1038/s41422-018-0052-4. Epub 2018 Jun 6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CRISPR-Associated Protein 9 / chemistry
  • CRISPR-Associated Protein 9 / metabolism*
  • CRISPR-Cas Systems*
  • Codon, Terminator / chemistry
  • Gene Editing / methods*
  • HEK293 Cells
  • Humans
  • Peptides / chemistry
  • Recombinant Fusion Proteins / chemistry

Substances

  • Codon, Terminator
  • Peptides
  • Recombinant Fusion Proteins
  • CRISPR-Associated Protein 9