Merkle, T. et al. Nat. Biotechnol. 37, 133–138 (2019).
Making changes in the genome after double-strand breaks in the DNA bears the risk of unintended mutations. Making changes by editing RNA, in contrast, involves no such breaks and is thus considered a safer method. Merkle et al. improve site-directed RNA editing by no longer relying on overexpression of the enzyme needed to introduce a base change, adenosine deaminase acting on RNA (ADAR), and instead recruiting endogenous enzymes. Their RESTORE method recruits the ADAR via a bipartite antisense oligo (ASO): an optimized hairpin binds to the enzyme, and a single-stranded sequence with chemical modifications binds the complementary RNA sequence of interest. The researchers show editing of several endogenous transcripts in cultured cell lines and disease-relevant loci in human primary cells. Off-target analysis by RNA-seq demonstrated high specificity of editing. While this work focuses on ADAR1, ASOs could be further modified to recruit other ADAR isoforms.
About this article
Cite this article
Rusk, N. RNA editing with endogenous ADARs. Nat Methods 16, 285 (2019). https://doi.org/10.1038/s41592-019-0380-4