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SMA is caused by deletions or mutations of <jats:italic>Survival Motor Neuron 1<\/jats:italic> (<jats:italic>SMN1<\/jats:italic>) gene. <jats:italic>SMN2<\/jats:italic>, a nearly identical copy of <jats:italic>SMN1<\/jats:italic>, cannot compensate for the loss of <jats:italic>SMN1<\/jats:italic> due to predominant skipping of exon 7. While various regulatory elements that modulate <jats:italic>SMN2<\/jats:italic> 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<jats:sup>\u2122<\/jats:sup> (synonyms: Nusinersen, IONIS-SMN<jats:sub>RX<\/jats:sub>, ISIS-SMN<jats:sub>RX<\/jats:sub>), an antisense drug based on ISS-N1 target. Spinraza<jats:sup>\u2122<\/jats:sup> 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<jats:sup>\u2122<\/jats:sup> 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<jats:sup>\u2122<\/jats:sup> 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.<\/jats:p>","DOI":"10.1515\/tnsci-2017-0001","type":"journal-article","created":{"date-parts":[[2017,2,5]],"date-time":"2017-02-05T10:06:04Z","timestamp":1486289164000},"page":"1-6","source":"Crossref","is-referenced-by-count":173,"title":["ISS-N1 makes the first FDA-approved drug for spinal muscular atrophy"],"prefix":"10.1515","volume":"8","author":[{"given":"Eric W.","family":"Ottesen","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences , Iowa State University , Ames , Iowa 50011 , United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2017,1,26]]},"reference":[{"key":"2024120612062964230_j_tnsci-2017-0001_ref_001_w2aab2b8ab1b7b1ab2b1b1Aa","doi-asserted-by":"crossref","unstructured":"Lunn M.R., Wang C.H., Spinal muscular atrophy. 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