Antisense Oligonucleotide Mediated Splice Correction of a Deep Intronic Mutation in OPA1.

ABSTRACT: Inherited optic neuropathies (ION) present an important cause of blindness in the European working-age population. Recently we reported the discovery of four independent families with deep intronic mutations in the main inherited optic neuropathies gene OPA1. These deep intronic mutations cause mis-splicing of the OPA1 pre-messenger-RNA transcripts by creating cryptic acceptor splice sites. As a rescue strategy we sought to prevent mis-splicing of the mutant pre-messenger-RNA by applying 2'O-methyl-antisense oligonucleotides (AONs) with a full-length phosphorothioate backbone that target the cryptic acceptor splice sites and the predicted novel branch point created by the deep intronic mutations, respectively. Transfection of patient-derived primary fibroblasts with these AONs induced corr

SUBMITTER: Bonifert T 

PROVIDER: S-EPMC5155325 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature