{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:00:23Z","timestamp":1792713623623,"version":"4.5.0"},"reference-count":42,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2014,3,10]],"date-time":"2014-03-10T00:00:00Z","timestamp":1394409600000},"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":[[2014,7]]},"abstract":"<jats:p>\n                    Spinal muscular atrophy (SMA) is a neuromuscular disease caused by mutations in survival motor neuron 1 (\n                    <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                    ). Previously, we showed that central nervous system (CNS) delivery of an adeno-associated viral (AAV) vector encoding\n                    <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                    produced significant improvements in survival in a mouse model of SMA. Here, we performed a dose\u2013response study in SMA mice to determine the levels of SMN in the spinal cord necessary for efficacy, and measured the efficiency of motor neuron transduction in the spinal cord after intrathecal delivery in pigs and nonhuman primates (NHPs). CNS injections of 5e10, 1e10, and 1e9 genome copies (gc) of self-complementary AAV9 (scAAV9)\u2013hSMN1 into SMA mice extended their survival from 17 to 153, 70, and 18 days, respectively. Spinal cords treated with 5e10, 1e10, and 1e9 gc showed that 70\u2013170%, 30\u2013100%, and 10\u201320% of wild-type levels of SMN were attained, respectively. Furthermore, detectable SMN expression in a minimum of 30% motor neurons correlated with efficacy. A comprehensive analysis showed that intrathecal delivery of 2.5e13 gc of scAAV9-GFP transduced 25\u201375% of the spinal cord motor neurons in NHPs. Thus, the extent of gene expression in motor neurons necessary to confer efficacy in SMA mice could be obtained in large-animal models, justifying the continual development of gene therapy for SMA.\n                  <\/jats:p>","DOI":"10.1089\/hum.2014.011","type":"journal-article","created":{"date-parts":[[2014,3,11]],"date-time":"2014-03-11T13:55:38Z","timestamp":1394546138000},"page":"619-630","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":93,"title":["Translational Fidelity of Intrathecal Delivery of Self-Complementary AAV9\u2013Survival Motor Neuron 1 for Spinal Muscular Atrophy"],"prefix":"10.1177","volume":"25","author":[{"given":"Marco A.","family":"Passini","sequence":"first","affiliation":[{"name":"Genzyme, a Sanofi Company"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Bu","sequence":"additional","affiliation":[{"name":"Genzyme, a Sanofi 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