Repair of CRISPR-guided RNA breaks enables site-specific RNA editing in human cells

Abstract

Genome editing with CRISPR RNA-guided endonucleases generates DNA breaks that are resolved by cellular DNA repair machinery. However, analogous methods to manipulate RNA remain unavailable. Here, we show that site-specific RNA breaks generated with RNA-targeting CRISPR complexes are repaired in human cells, and this repair can be used for programmable deletions in human transcripts that restore gene function. Collectively, this work establishes a technology for precise RNA manipulation with potential therapeutic applications.One-Sentence SummaryCRISPR-guided RNA breaks are repaired in human cells, and this RNA repair can be used for programmable editing of human transcriptomes.