Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage

Komor et al. (2016). Nature DOI: 10.1038/nature17946 Citations: 5419

HDR-based point mutation correction was inefficient and indel-prone. This paper fused cytidine deaminase to dead Cas9, adding UGI and a nickase to create BE3 for C-to-T editing. BE3 converted up to 37% of alleles with about 1% indels, correcting APOE4 to APOE3r in astrocytes.

Parts used

BE3

Key findings

  • First cytosine base editor (BE3) fusing rat APOBEC1 to Cas9 nickase with UGI. Achieved >30% C-to-T editing efficiency with only 1.1% average indel frequency across multiple human cell line targets.