Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors.

ABSTRACT: CRISPR-Cas base-editor technology enables targeted nucleotide alterations, and is being increasingly used for research and potential therapeutic applications^1,2. The most widely used cytosine base editors (CBEs) induce deamination of DNA cytosines using the rat APOBEC1 enzyme, which is targeted by a linked Cas protein-guide RNA complex^3,4. Previous studies of the specificity of CBEs have identified off-target DNA edits in mammalian cells^5,6. Here we show that a CBE with rat APOBEC1 can cause extensive transcriptome-wide deamination of RNA cytosines in human cells, inducing tens of thousands of C-to-U edits with frequencies ranging from 0.07% to 100% in 38-58% of expressed genes. CBE-induced RNA edits occur in both protein-coding and non-protein-coding seque

SUBMITTER: Grunewald J 

PROVIDER: S-EPMC6657343 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature