{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:47:53Z","timestamp":1791042473276,"version":"4.1.0"},"reference-count":63,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2010,12,16]],"date-time":"2010-12-16T00:00:00Z","timestamp":1292457600000},"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":[[2011,2]]},"abstract":"<jats:p>\n                    Spinal muscular atrophy (SMA), a neurodegenerative disease, is the second most common genetic disorder and the leading genetic cause of infantile death. SMA arises from the loss of\n                    <jats:italic toggle=\"yes\">Survival Motor Neuron-1<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                    ), leading to degeneration of lower motor neurons and, consequently, the atrophy of voluntary muscles. A duplicated copy gene called\n                    <jats:italic toggle=\"yes\">SMN2<\/jats:italic>\n                    exists in humans.\n                    <jats:italic toggle=\"yes\">SMN2<\/jats:italic>\n                    is unable to fully compensate for the loss of\n                    <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                    because it produces very low levels of functional SMN protein due to an alternative splicing event. A C\/T transition in\n                    <jats:italic toggle=\"yes\">SMN2<\/jats:italic>\n                    exon 7 results in a transcript lacking exon 7 and, therefore, creates a truncated SMN protein that cannot fully compensate for the loss of\n                    <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                    . However,\n                    <jats:italic toggle=\"yes\">SMN2<\/jats:italic>\n                    is an ideal target for therapeutic strategies that redirect this critical splicing event. Previously, we developed the first\n                    <jats:italic toggle=\"yes\">trans<\/jats:italic>\n                    -splicing strategy to increase the full-length mRNA and functional SMN protein from the\n                    <jats:italic toggle=\"yes\">SMN2<\/jats:italic>\n                    gene. To improve the\n                    <jats:italic toggle=\"yes\">trans<\/jats:italic>\n                    -splicing efficacy, we then developed a single-vector system that expressed a\n                    <jats:italic toggle=\"yes\">trans<\/jats:italic>\n                    -splicing RNA (tsRNA) and an antisense blocking the downstream splice site. This single vector greatly enhanced\n                    <jats:italic toggle=\"yes\">trans<\/jats:italic>\n                    -splicing of\n                    <jats:italic toggle=\"yes\">SMN2<\/jats:italic>\n                    transcripts\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    . In this report, we have added a neurotrophic factor [insulin-like growth factor (IGF)-1] to this single vector to determine whether neuroprotection and SMN induction provide greater protection in an SMA animal model. Intracerebroventricular injection of the\n                    <jats:italic toggle=\"yes\">trans<\/jats:italic>\n                    -splicing\/IGF vector significantly increased SMN protein in brain and spinal cord of SMA\u03947 mice and lessened the severity of disease in a more severe mouse model as evidenced by an extension of life span and increased body mass.\n                  <\/jats:p>","DOI":"10.1089\/hum.2010.114","type":"journal-article","created":{"date-parts":[[2010,8,30]],"date-time":"2010-08-30T16:53:46Z","timestamp":1283187226000},"page":"135-144","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":70,"title":["Combination of SMN\n                    <i>Trans<\/i>\n                    -Splicing and a Neurotrophic Factor Increases the Life Span and Body Mass in a Severe Model of Spinal Muscular Atrophy"],"prefix":"10.1177","volume":"22","author":[{"given":"Monir","family":"Shababi","sequence":"first","affiliation":[{"name":"University of Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Glascock","sequence":"additional","affiliation":[{"name":"University of Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian L.","family":"Lorson","sequence":"additional","affiliation":[{"name":"University of Missouri"},{"name":"University of Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2010,12,16]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2006.01.012"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp076"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2008.03481.x"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200108080-00048"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/146608201316949523"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2004.02.042"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/360692a0"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.11.148"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.21.12185"},{"key":"e_1_3_3_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.15.8745"},{"key":"e_1_3_3_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm900"},{"key":"e_1_3_3_13_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4489-09.2010"},{"key":"e_1_3_3_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300222"},{"key":"e_1_3_3_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0003468"},{"key":"e_1_3_3_16_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1996.0010"},{"key":"e_1_3_3_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-005-0912-y"},{"key":"e_1_3_3_18_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2008.067"},{"key":"e_1_3_3_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2008.60"},{"key":"e_1_3_3_20_1","first-page":"326","article-title":"Rediscovering an old friend, IGF-I: potential use in the treatment of neurodegenerative diseases","volume":"20","author":"Dore S.","year":"1997","unstructured":"Dore S., , Kar S., , Quirion R. 1997. Rediscovering an old friend, IGF-I: potential use in the treatment of neurodegenerative diseases. 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