Singh, Natalia N.Shishimorova, MariaCao, Lu ChengGangwani, LaxmanSingh, Ravindra N.2022-08-232022-08-232009-05-122010-04-07RNA Biol. 2009 Jul;6(3):341-50. Epub 2009 Jul 14. <a href="http://dx.doi.org/10.4161/rna.6.3.8723">Link to article on publisher's website</a>1547-6286 (Linking)10.4161/rna.6.3.872319430205https://hdl.handle.net/20.500.14038/39417Spinal muscular atrophy (SMA) is the leading genetic cause of infant mortality. Most SMA cases are associated with the low levels of SMN owing to deletion of Survival Motor Neuron 1 (SMN1). SMN2, a nearly identical copy of SMN1, fails to compensate for the loss of SMN1 due to predominant skipping of exon 7. Hence, correction of aberrant splicing of SMN2 exon 7 holds the potential for cure of SMA. Here we report an 8-mer antisense oligonucleotide (ASO) to have a profound stimulatory response on correction of aberrant splicing of SMN2 exon 7 by binding to a unique GC-rich sequence located within intron 7 of SMN2. We confirm that the splicing-switching ability of this short ASO comes with a high degree of specificity and reduced off-target effect compared to larger ASOs targeting the same sequence. We further demonstrate that a single low nanomolar dose of this 8-mer ASO substantially increases the levels of SMN and a host of factors including Gemin 2, Gemin 8, ZPR1, hnRNP Q and Tra2-beta1 known to be down-regulated in SMA. Our findings underscore the advantages and unmatched potential of very short ASOs in splicing modulation in vivo.en-USBase PairingBase SequenceCell LineDown-RegulationExonsHumansIntronsMuscular Atrophy, SpinalOligonucleotides, AntisenseRNA SplicingSurvival of Motor Neuron 2 ProteinBiochemistry, Biophysics, and Structural BiologyLife SciencesMedicine and Health SciencesJournal Articlehttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3211&amp;context=oapubs&amp;unstamped=1https://escholarship.umassmed.edu/oapubs/22121264544oapubs/2212