Targeting the 5′ untranslated region of SMN2 as a therapeutic strategy for spinal muscular atrophy
Audrey M. Winkelsas, Christopher Grunseich, George G. Harmison, Katarzyna Chwalenia, Carlo Rinaldi, Suzan M. Hammond, Kory Johnson, Mélissa Bowerman, Sukrat Arya, Kevin Talbot, Matthew J. A. Wood, Kenneth H. Fischbeck
Abstract
mRNA decay. Moreover, use of the 5' UTR ASO in combination with a splice-switching oligonucleotide (SSO) increases SMN levels above those attained with the SSO alone. Our results add to the current understanding of SMN regulation and point toward a new therapeutic target for SMA.
Topics & Concepts
SMN1Spinal muscular atrophyExonSMA*Untranslated regionFive prime untranslated regionRNA splicingBiologyAlternative splicingGeneThree prime untranslated regionMessenger RNAMolecular biologyGeneticsRNAMathematicsCombinatoricsNeurogenetic and Muscular Disorders ResearchRNA modifications and cancerRNA Interference and Gene Delivery