In vivo RNA editing of point mutations via RNA-guided adenosine deaminases

Nat Methods. 2019 Mar;16(3):239-242. doi: 10.1038/s41592-019-0323-0. Epub 2019 Feb 8.

Abstract

We present in vivo sequence-specific RNA base editing via adenosine deaminases acting on RNA (ADAR) enzymes with associated ADAR guide RNAs (adRNAs). To achieve this, we systematically engineered adRNAs to harness ADARs, and comprehensively evaluated the specificity and activity of the toolsets in vitro and in vivo via two mouse models of human disease. We anticipate that this platform will enable tunable and reversible engineering of cellular RNAs for diverse applications.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Deaminase / metabolism*
  • Animals
  • Disease Models, Animal
  • HEK293 Cells
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mice
  • Point Mutation*
  • RNA Editing*
  • RNA Splicing
  • RNA, Guide / metabolism*
  • RNA, Messenger / genetics

Substances

  • RNA, Guide
  • RNA, Messenger
  • Adenosine Deaminase