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

Science. 2024 May 17;384(6697):808-814. doi: 10.1126/science.adk5518. Epub 2024 Apr 25.

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. We show that site-specific RNA breaks generated with type-III CRISPR complexes are repaired in human cells and that this repair can be used for programmable deletions in human transcripts to restore gene function. Collectively, this work establishes a technology for precise RNA manipulation with potential therapeutic applications.

MeSH terms

  • CRISPR-Associated Proteins*
  • CRISPR-Cas Systems*
  • Cyclophilins / genetics
  • DNA Repair
  • Endonucleases / metabolism
  • Gene Editing* / methods
  • HEK293 Cells
  • Humans
  • Protein Deglycase DJ-1 / genetics
  • RNA* / genetics
  • RNA, Guide, CRISPR-Cas Systems* / genetics
  • Streptococcus thermophilus

Substances

  • Endonucleases
  • RNA
  • RNA, Guide, CRISPR-Cas Systems
  • CRISPR-Associated Proteins
  • cyclophilin B
  • PARK7 protein, human
  • Protein Deglycase DJ-1
  • Cyclophilins