Global quantification exposes abundant low-level off-target activity by base editors.

ABSTRACT: Base editors are dedicated engineered deaminases that enable directed conversion of specific bases in the genome or transcriptome in a precise and efficient manner, and hold promise for correcting pathogenic mutations. A major concern limiting application of this powerful approach is the issue of off-target edits. Several recent studies have shown substantial off-target RNA activity induced by base editors and demonstrated that off-target mutations may be suppressed by improved deaminases versions or optimized guide RNAs. Here, we describe a new class of off-target events that are invisible to the established methods for detection of genomic variations and were thus far overlooked. We show that nonspecific, seemingly stochastic, off-target events affect a large number of sites throughout t

SUBMITTER: Buchumenski I 

PROVIDER: S-EPMC8647836 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature