SPLICER: a highly efficient base editing toolbox that enables in vivo therapeutic exon skipping.

ABSTRACT: Exon skipping technologies enable exclusion of targeted exons from mature mRNA transcripts, which have broad applications in medicine and biotechnology. Existing techniques including antisense oligonucleotides, targetable nucleases, and base editors, while effective for specific applications, remain hindered by transient effects, genotoxicity, and inconsistent exon skipping. To overcome these limitations, here we develop SPLICER, a toolbox of next-generation base editors containing near-PAMless Cas9 nickase variants fused to adenosine or cytosine deaminases for the simultaneous editing of splice acceptor (SA) and splice donor (SD) sequences. Synchronized SA and SD editing improves exon skipping, reduces aberrant splicing, and enables skipping of exons refractory to single splice site editi

SUBMITTER: Miskalis A 

PROVIDER: S-EPMC11604662 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature