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

By Luke W. Koblan, Jordan L. Doman, Christopher Wilson, Jonathan M. Levy, Tristan Tay, Gregory A. Newby, J. P. Maianti, Aditya Raguram, David R. Liu. Nature Biotechnology, 2018

835 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/059f5d2175059bc74ce84cee3e82c1b103ebcc76

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In Molecular Biology

1. Gregory A. Newby
2. Aditya Raguram
3. Jordan L. Doman
4. David R. Liu
5. Caixia Gao

Citations in the corpus

• Evaluation and Minimization of Cas9-Independent Off-Target DNA Editing by Cytosine Base Editors (2020, positive): “Indeed, high-throughput sequencing of six dSaCas9 loci three days after plasmid cotransfection resulted in off-target deamination by APOBEC1-based BE4 4,35 that was easily detected by targeted DNA sequencing (0.4–25%), and were independent of the on-target SpCas9 guide RNA (Fig.”