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

Luke W. Koblan, Jordan L. Doman, Christopher Wilson, Jonathan M. Levy, Tristan Tay, Gregory A. Newby, Juan Pablo Maianti, Aditya Raguram, David R. Liu

Research output: Contribution to journalArticlepeer-review

375 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)843-848
Number of pages6
JournalNature biotechnology
Volume36
Issue number9
DOIs
StatePublished - Oct 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

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