DMD antisense oligonucleotide mediated exon skipping efficiency correlates with flanking intron retention time and target position within the exon.

ABSTRACT: Mutations in the DMD gene are causative for Duchenne muscular dystrophy (DMD). Antisense oligonucleotide (AON) mediated exon skipping to restore disrupted dystrophin reading frame is a therapeutic approach that allows production of a shorter but functional protein. As DMD causing mutations can affect most of the 79 exons encoding dystrophin, a wide variety of AONs are needed to treat the patient population. Design of AONs is largely guided by trial-and-error, and it is yet unclear what defines the skippability of an exon. Here, we use a library of phosphorodiamidate morpholino oligomer (PMOs) AONs of similar physical properties to test the skippability of a large number of DMD exons. The DMD transcript is non-sequentially spliced, meaning that certain introns are retai

SUBMITTER: Goossens R 

PROVIDER: S-EPMC10481881 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature