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Improving cytidine and adenine base editors by expression optimization and ancestral reconstruction.

Luke W KoblanJordan L DomanChristopher WilsonJonathan M LevyTristan TayGregory A NewbyJuan Pablo MaiantiAditya RaguramDavid R Liu
Published in: Nature biotechnology (2018)
Base editors enable targeted single-nucleotide conversions in genomic DNA. Here we show that expression levels are a bottleneck in base-editing efficiency. We optimize cytidine (BE4) and adenine (ABE7.10) base editors by modification of nuclear localization signals (NLS) and codon usage, and ancestral reconstruction of the deaminase component. The resulting BE4max, AncBE4max, and ABEmax editors correct pathogenic SNPs with substantially increased efficiency in a variety of mammalian cell types.
Keyphrases
  • poor prognosis
  • crispr cas
  • single cell
  • binding protein
  • gene expression
  • genome wide
  • single molecule
  • stem cells
  • copy number