{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:51:18Z","timestamp":1791341478641,"version":"4.3.1"},"reference-count":63,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2013,1,21]],"date-time":"2013-01-21T00:00:00Z","timestamp":1358726400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:p>\n                    In the search for the most efficacious antisense oligonucleotides (AOs) aimed at inducing\n                    <jats:italic toggle=\"yes\">SMN2<\/jats:italic>\n                    exon 7 inclusion, we systematically assessed three AOs, PMO25 (\u221210, \u221234), PMO18 (\u221210, \u221227), and PMO20 (\u221210, \u221229), complementary to the\n                    <jats:italic toggle=\"yes\">SMN2<\/jats:italic>\n                    intron 7 splicing silencer (ISS-N1). PMO25 was the most efficacious in augmenting exon 7 inclusion\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    in spinal muscular atrophy (SMA) patient fibroblasts and\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    splicing assays. PMO25 and PMO18 were compared further in a mouse model of severe SMA. After a single intracerebroventricular (ICV) injection in neonatal mice, PMO25 increased the life span of severe SMA mice up to 30-fold, with average survival greater by 3-fold compared with PMO18 at a dose of 20\u2009\u03bcg\/g and 2-fold at 40\u2009\u03bcg\/g. Exon 7 inclusion was increased in the CNS but not in peripheral tissues. Systemic delivery of PMO25 at birth achieved a similar outcome and produced increased exon 7 inclusion both in the CNS and peripherally. Systemic administration of a 10-\u03bcg\/g concentration of PMO25 conjugated to an octaguanidine dendrimer (VMO25) increased the life span only 2-fold in neonatal type I SMA mice, although it prevented tail necrosis in mild SMA mice. Higher doses and ICV injection of VMO25 were associated with toxicity. We conclude that (1) the 25-mer AO is more efficient than the 18-mer and 20-mer in modifying\n                    <jats:italic toggle=\"yes\">SMN2<\/jats:italic>\n                    splicing\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    ; (2) it is more efficient in prolonging survival in SMA mice; and (3) naked Morpholino oligomers are more efficient and safer than the Vivo-Morpholino and have potential for future SMA clinical applications.\n                  <\/jats:p>","DOI":"10.1089\/hum.2012.211","type":"journal-article","created":{"date-parts":[[2013,1,22]],"date-time":"2013-01-22T14:33:41Z","timestamp":1358865221000},"page":"331-342","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":117,"title":["A Novel Morpholino Oligomer Targeting ISS-N1 Improves Rescue of Severe Spinal Muscular Atrophy Transgenic Mice"],"prefix":"10.1177","volume":"24","author":[{"given":"Haiyan","family":"Zhou","sequence":"first","affiliation":[{"name":"University College London","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narinder","family":"Janghra","sequence":"additional","affiliation":[{"name":"University College London","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chalermchai","family":"Mitrpant","sequence":"additional","affiliation":[{"name":"Mahidol University","place":["Thailand"]},{"name":"University of Western Australia","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel L.","family":"Dickinson","sequence":"additional","affiliation":[{"name":"University of Leicester","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Anthony","sequence":"additional","affiliation":[{"name":"University College London","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loren","family":"Price","sequence":"additional","affiliation":[{"name":"University of Western Australia","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian C.","family":"Eperon","sequence":"additional","affiliation":[{"name":"University of Leicester","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D.","family":"Wilton","sequence":"additional","affiliation":[{"name":"University of Western Australia","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Morgan","sequence":"additional","affiliation":[{"name":"University College London","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Muntoni","sequence":"additional","affiliation":[{"name":"University College London","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2013,1,21]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1089\/oli.2009.0215"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr148"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2009.01.071"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29562"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp076"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng854"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsb887"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60756-3"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awp318"},{"key":"e_1_3_3_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq514"},{"key":"e_1_3_3_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.18.8673"},{"key":"e_1_3_3_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.7.1083"},{"key":"e_1_3_3_14_1","doi-asserted-by":"publisher","DOI":"10.1086\/338627"},{"key":"e_1_3_3_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1610"},{"key":"e_1_3_3_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp313"},{"key":"e_1_3_3_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm379"},{"key":"e_1_3_3_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1011367"},{"key":"e_1_3_3_19_1","first-page":"517","article-title":"Molecular and phenotypic reassessment of an infrequently used mouse model for spinal muscular atrophy","volume":"39","author":"Gogliotti R.G.","year":"2009","unstructured":"Gogliotti R.G., , Hammond S.M., , Lutz C., , DiDonato C.J. 2009. 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