{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:21:06Z","timestamp":1792707666518,"version":"4.5.0"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,6,16]],"date-time":"2017-06-16T00:00:00Z","timestamp":1497571200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,6,16]],"date-time":"2017-06-16T00:00:00Z","timestamp":1497571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Spinal muscular atrophy (SMA) is an autosomal recessive disorder affecting motor neurons, and is currently the most frequent genetic cause of infant mortality. SMA is caused by a loss-of-function mutation in the <jats:italic>survival motor neuron 1<\/jats:italic> (<jats:italic>SMN1<\/jats:italic>) gene. <jats:italic>SMN2<\/jats:italic> is an <jats:italic>SMN1<\/jats:italic> paralogue, but cannot compensate for the loss of <jats:italic>SMN1<\/jats:italic> since exon 7 in <jats:italic>SMN2<\/jats:italic> mRNA is excluded (spliced out) due to a single C-to-T nucleotide transition in the exon 7. One of the most promising strategies to treat SMA is antisense oligonucleotide (AON)-mediated therapy. AONs are utilized to block intronic splicing silencer number 1 (ISS-N1) on intron 7 of <jats:italic>SMN2<\/jats:italic>, which causes exon 7 inclusion of the mRNA and the recovery of the expression of functional SMN protein from the endogenous <jats:italic>SMN2<\/jats:italic> gene. We developed novel locked nucleic acid (LNA)-based antisense oligonucleotides (LNA\/DNA mixmers), which efficiently induce exon 7 inclusion in <jats:italic>SMN2<\/jats:italic> and restore the SMN protein production in SMA patient fibroblasts. The mixmers are highly specific to the targeted sequence, and showed significantly higher efficacy than an all-LNA oligonucleotide with the equivalent sequence. These data suggest that use of LNA\/DNA mixmer-based AONs may be an attractive therapeutic strategy to treat SMA.<\/jats:p>","DOI":"10.1038\/s41598-017-03850-2","type":"journal-article","created":{"date-parts":[[2017,6,12]],"date-time":"2017-06-12T09:59:11Z","timestamp":1497261551000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["LNA\/DNA mixmer-based antisense oligonucleotides correct alternative splicing of the\u00a0SMN2 gene and restore SMN protein expression in type 1 SMA fibroblasts"],"prefix":"10.1038","volume":"7","author":[{"given":"Aleksander","family":"Touznik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rika","family":"Maruyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kana","family":"Hosoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Echigoya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshifumi","family":"Yokota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,6,16]]},"reference":[{"key":"3850_CR1","doi-asserted-by":"publisher","first-page":"04","DOI":"10.12703\/P7-04","volume":"7","author":"DM Iascone","year":"2015","unstructured":"Iascone, D. 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