Global Quantification Exposes Most DNA & RNA Off-Target Activity by Base Editors is Non-Specific

Time: 2:00 pm
day: Day One


• Off-target edits are a major concern limiting the application of base editors. Multiple studies have been dedicated to identification of these events and further enzyme optimization to suppress them
• These studies have mainly focused on strongly edited off-target sites, where editing affects an appreciable fraction (>10%) of transcripts. We point out that the majority of off-target activity of the deaminases is nonspecific, seemingly stochastic, and deaminates a large number of sites throughout the genome or the transcriptome, at a low editing probability per site per molecule
• Here we employ a complementary computational approach that is sensitive to the stochastic off-targets activity, and show that off-target RNA and DNA mutations are abundant even for current optimized deaminase editors. We provide a computational tool to quantify global off-target activity, which can be used to optimize future base editors