Spinal muscular atrophy (SMA) is one of the leading genetic diseases of children 
and infants. SMA is caused by deletions or mutations of Survival Motor Neuron 1 
(SMN1) gene. SMN2, a nearly identical copy of SMN1, cannot compensate for the 
loss of SMN1 due to predominant skipping of exon 7. While various regulatory 
elements that modulate SMN2 exon 7 splicing have been proposed, intronic 
splicing silencer N1 (ISS-N1) has emerged as the most promising target thus far 
for antisense oligonucleotide-mediated splicing correction in SMA. Upon 
procuring exclusive license from the University of Massachussets Medical School 
in 2010, Ionis Pharmaceuticals (formerly ISIS Pharamaceuticals) began clinical 
development of Spinraza™ (synonyms: Nusinersen, IONIS-SMNRX, ISIS-SMNRX), an 
antisense drug based on ISS-N1 target. Spinraza™ showed very promising results 
at all steps of the clinical development and was approved by US Food and Drug 
Administration (FDA) on December 23, 2016. Spinraza™ is the first FDA-approved 
treatment for SMA and the first antisense drug to restore expression of a fully 
functional protein via splicing correction. The success of Spinraza™ underscores 
the potential of intronic sequences as promising therapeutic targets and sets 
the stage for further improvement of antisense drugs based on advanced 
oligonucleotide chemistries and delivery protocols.