{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T16:56:44Z","timestamp":1792601804943,"version":"4.5.0"},"reference-count":38,"publisher":"Society for Neuroscience","issue":"1","license":[{"start":{"date-parts":[[2010,7,6]],"date-time":"2010-07-06T00:00:00Z","timestamp":1278374400000},"content-version":"vor","delay-in-days":181,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2010,1,6]]},"abstract":"<jats:p>Spinal muscular atrophy is a leading genetic cause of infantile death and occurs in \u223c1\/6000 live births. SMA is caused by the loss of<jats:italic>Survival Motor Neuron-1<\/jats:italic>(<jats:italic>SMN1<\/jats:italic>), however, all patients retain at least one copy of a nearly identical gene called<jats:italic>SMN2<\/jats:italic>. While<jats:italic>SMN2<\/jats:italic>and<jats:italic>SMN1<\/jats:italic>are comprised of identical coding sequences, the majority of<jats:italic>SMN2<\/jats:italic>transcripts are alternatively spliced, encoding a truncated protein that is unstable and nonfunctional. Considerable effort has focused upon modulating the<jats:italic>SMN2<\/jats:italic>alternative splicing event since this would produce more wild-type protein. Recently we reported the development of an optimized<jats:italic>trans<\/jats:italic>-splicing system that involved the coexpression of a<jats:italic>SMN2 trans<\/jats:italic>-splicing RNA and an antisense RNA that blocks a downstream splice site in<jats:italic>SMN2<\/jats:italic>pre-mRNA. Here, we demonstrate that<jats:italic>in vivo<\/jats:italic>delivery of the optimized<jats:italic>trans<\/jats:italic>-splicing vector increases an important SMN-dependent activity, snRNP assembly, in disease-relevant tissue in the SMA mouse model. A single injection of the vector into the intracerebral-ventricular space in SMA neonates also lessens the severity of the SMA phenotype in a severe SMA mouse model, extending survival \u223c70%. Collectively, these results provide the first<jats:italic>in vivo<\/jats:italic>demonstration that<jats:italic>SMN2 trans<\/jats:italic>-splicing leads to a lessening of the severity of the SMA phenotype and provide evidence for the power of this strategy for reprogramming genetic diseases at the pre-mRNA level.<\/jats:p>","DOI":"10.1523\/jneurosci.4489-09.2010","type":"journal-article","created":{"date-parts":[[2010,1,6]],"date-time":"2010-01-06T17:32:42Z","timestamp":1262799162000},"page":"126-130","source":"Crossref","is-referenced-by-count":87,"title":["<i>Trans<\/i>-Splicing-Mediated Improvement in a Severe Mouse Model of Spinal Muscular Atrophy"],"prefix":"10.1523","volume":"30","author":[{"given":"Tristan H.","family":"Coady","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian 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