Heat increases full-length SMN splicing: promise for splice-augmenting therapies for SMA.

ABSTRACT: Spinal muscular atrophy (SMA) is a debilitating neurodegenerative pediatric disease characterized by low levels of the survival motor protein (SMN). Humans have two SMN genes that produce identical SMN proteins, but they differ at a key nucleotide in exon 7 that induces differential mRNA splicing. SMN1 primarily produces full-length SMN protein, but due to the spliceosome's inability to efficiently recognize exon 7, SMN2 transcripts are often truncated. SMA occurs primarily through mutations or deletions in the SMN1 gene; therefore, current therapies use antisense oligonucleotides (ASOs) to target exon 7 inclusion in SMN2 mRNA and promote full-length SMN protein production. Here, we explore additional methods that can target SMN splicing and therapeutically increase full-length SMN protein

SUBMITTER: Dominguez CE 

PROVIDER: S-EPMC12361924 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature