{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T12:52:55Z","timestamp":1792759975251,"version":"4.5.0"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2020,2,27]],"date-time":"2020-02-27T00:00:00Z","timestamp":1582761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81271423"],"award-info":[{"award-number":["81271423"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81471298"],"award-info":[{"award-number":["81471298"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81530035"],"award-info":[{"award-number":["81530035"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["GM42699"],"award-info":[{"award-number":["GM42699"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Spinal muscular atrophy (SMA) is a motor neuron disease. Nusinersen, a splice-switching antisense oligonucleotide (ASO), was the first approved drug to treat SMA. Based on prior preclinical studies, both 2\u2032-O-methoxyethyl (MOE) with a phosphorothioate backbone and morpholino with a phosphorodiamidate backbone\u2014with the same or extended target sequence as nusinersen\u2014displayed efficient rescue of SMA mouse models. Here, we compared the therapeutic efficacy of these two modification chemistries in rescue of a severe mouse model using ASO10-29\u2014a 2-nt longer version of nusinersen\u2014via subcutaneous injection. Although both chemistries efficiently corrected SMN2 splicing in various tissues, restored motor function and improved the integrity of neuromuscular junctions, MOE-modified ASO10-29 (MOE10-29) was more efficacious than morpholino-modified ASO10-29 (PMO10-29) at the same molar dose, as seen by longer survival, greater body-weight gain and better preservation of motor neurons. Time-course analysis revealed that MOE10-29 had more persistent effects than PMO10-29. On the other hand, PMO10-29 appears to more readily cross an immature blood-brain barrier following systemic administration, showing more robust initial effects on SMN2 exon 7 inclusion, but less persistence in the central nervous system. We conclude that both modifications can be effective as splice-switching ASOs in the context of SMA and potentially other diseases, and discuss the advantages and disadvantages of each.<\/jats:p>","DOI":"10.1093\/nar\/gkaa126","type":"journal-article","created":{"date-parts":[[2020,2,19]],"date-time":"2020-02-19T15:40:12Z","timestamp":1582126812000},"page":"2853-2865","source":"Crossref","is-referenced-by-count":85,"title":["Comparison of the efficacy of MOE and PMO modifications of systemic antisense oligonucleotides in a severe SMA mouse model"],"prefix":"10.1093","volume":"48","author":[{"given":"Lei","family":"Sheng","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China"},{"name":"Department of Orthopedics, the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China"},{"name":"Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, New York, NY 11724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Rigo","sequence":"first","affiliation":[{"name":"Ionis Pharmaceuticals, Carlsbad, CA\u00a092010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C Frank","family":"Bennett","sequence":"first","affiliation":[{"name":"Ionis Pharmaceuticals, Carlsbad, CA\u00a092010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1110-8688","authenticated-orcid":false,"given":"Adrian R","family":"Krainer","sequence":"first","affiliation":[{"name":"Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, New York, NY 11724, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0905-7989","authenticated-orcid":false,"given":"Yimin","family":"Hua","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing 210023, China"},{"name":"Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, New York, NY 11724, USA"},{"name":"Institute of Neuroscience, Soochow University, 199 Ren-Ai Road, Suzhou, Jiangsu 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,2,27]]},"reference":[{"key":"2020032822063262400_B1","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1126\/science.165.3898.1137","article-title":"[Interferon induction increased through chemical modification of a synthetic polyribonucleotide]","volume":"165","author":"De\u00a0Clercq","year":"1969","journal-title":"Science (New York, N.Y.)"},{"key":"2020032822063262400_B2","doi-asserted-by":"crossref","first-page":"3209","DOI":"10.1093\/nar\/16.8.3209","article-title":"Physicochemical properties of phosphorothioate oligodeoxynucleotides","volume":"16","author":"Stein","year":"1988","journal-title":"Nucleic Acids Res."},{"key":"2020032822063262400_B3","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/9304","article-title":"Crystal structure and improved antisense properties of 2\u2032-O-(2-methoxyethyl)-RNA","volume":"6","author":"Teplova","year":"1999","journal-title":"Nat. Struct. Biol."},{"key":"2020032822063262400_B4","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1093\/nass\/nrn280","article-title":"Design, synthesis and evaluation of constrained methoxyethyl (cMOE) and constrained ethyl (cEt) nucleoside analogs","volume":"2004","author":"Seth","year":"2008","journal-title":"Nucleic Acids Symp. Ser."},{"key":"2020032822063262400_B5","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1016\/S0960-894X(98)00366-7","article-title":"The first analogues of LNA (locked nucleic acids): phosphorothioate-LNA and 2\u2032-thio-LNA","volume":"8","author":"Kumar","year":"1998","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2020032822063262400_B6","doi-asserted-by":"crossref","first-page":"10962","DOI":"10.1073\/pnas.1605731113","article-title":"Systemic peptide-mediated oligonucleotide therapy improves long-term survival in spinal muscular atrophy","volume":"113","author":"Hammond","year":"2016","journal-title":"Proc. Natl. Acad. Sci. 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