{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:02:21Z","timestamp":1791928941245,"version":"4.3.4"},"reference-count":51,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T00:00:00Z","timestamp":1668038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T00:00:00Z","timestamp":1668038400000},"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":["Nucleic Acid Therapeutics"],"published-print":{"date-parts":[[2023,2,1]]},"abstract":"<jats:p>\n                    SHANK3 is a member of the SHANK family of scaffolding proteins that localize to the postsynaptic density of excitatory synapses. Mutations within the\n                    <jats:italic toggle=\"yes\">SHANK3<\/jats:italic>\n                    gene or\n                    <jats:italic toggle=\"yes\">SHANK3<\/jats:italic>\n                    haploinsufficiency is thought to be one of the major causes for Phelan-McDermid Syndrome (PMDS) that is characterized by a broad spectrum of autism-related behavioral alterations. Several approaches have already been proposed to elevate SHANK3 protein levels in PMDS patients like transcriptional activation or inhibition of SHANK3 degradation. We undertook a systematic screening approach and tested whether defined antisense oligonucleotides (ASOs) directed against the 3\u2032 untranslated region (3\u2032-UTR) of the human\n                    <jats:italic toggle=\"yes\">SHANK3<\/jats:italic>\n                    mRNA are suitable to elevate SHANK3 protein levels. Using human induced pluripotent stem cells (hiPSCs) and hiPSCs-derived motoneurons from controls and PMDS patients we eventually identified two 18 nucleotide ASOs (ASO 4-5.2-4 and 4-5.2-6) that were able to increase SHANK3 protein levels\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    by about 1.3- to 1.6-fold. These findings were confirmed by co-transfection of the identified ASOs with a GFP-SHANK3-3\u2032-UTR construct in HEK293T cells using GFP protein expression as read-out. Based on these results we propose a novel approach to elevate SHANK3 protein concentrations by 3\u2032-UTR specific ASOs. Further research is needed to test the suitability of\n                    <jats:italic toggle=\"yes\">SHANK3<\/jats:italic>\n                    -specific ASOs as pharmacological compounds also\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1089\/nat.2022.0048","type":"journal-article","created":{"date-parts":[[2022,11,10]],"date-time":"2022-11-10T11:11:47Z","timestamp":1668078707000},"page":"58-71","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Elevation of SHANK3 Levels by Antisense Oligonucleotides Directed Against the 3\u2032-UTR of the Human\n                    <i>SHANK3<\/i>\n                    mRNA"],"prefix":"10.1177","volume":"33","author":[{"given":"Nadine","family":"Stirmlinger","sequence":"first","affiliation":[{"name":"Institute of Anatomy and Cell Biology and Ulm University, Ulm, Germany."},{"name":"International Graduate School for Molecular Medicine, Ulm University, Ulm, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8831-858X","authenticated-orcid":false,"given":"Jan Philip","family":"Delling","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology and Ulm University, Ulm, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Pf\u00e4nder","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology and Ulm University, Ulm, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1486-8535","authenticated-orcid":false,"given":"Tobias M.","family":"Boeckers","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell Biology and Ulm University, Ulm, Germany."},{"name":"DZNE, Ulm Site, Ulm, 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