QBEmax is a sequence-permuted and internally protected base editor

Abstract

Cytosine base editors (CBEs) show promise for multiplex gene knockout applications, but impure edits, indels and off-targets still frequently occur. We describe here QBEmax, which exhibits high efficiency, low indel and off-targets and high product purity with up to 99.8% of edits comprised of C-to-T. Through molecular dynamic modeling, QBEmax presents as a compact and stable base editor that shields protected bases from undesired repair processes. A base editor designed using circular permutation reduces off-target effects while enhancing purity.

Topics & Concepts