Targeting the 5' untranslated region of <i>SMN2</i> as a therapeutic strategy for spinal muscular atrophy.

ABSTRACT: Spinal muscular atrophy (SMA) is a neuromuscular disorder caused by mutations in the survival motor neuron 1 (SMN1) gene. All patients have at least one copy of a paralog, SMN2, but a C-to-T transition in this gene results in exon 7 skipping in a majority of transcripts. Approved treatment for SMA involves promoting exon 7 inclusion in the SMN2 transcript or increasing the amount of full-length SMN by gene replacement with a viral vector. Increasing the pool of SMN2 transcripts and increasing their translational efficiency can be used to enhance splice correction. We sought to determine whether the 5' untranslated region (5' UTR) of SMN2 contains a repressive feature that can be targeted to increase SMN levels. We found that antisense oligonucleotides (AS

SUBMITTER: Winkelsas AM 

PROVIDER: S-EPMC7851419 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature