{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:26:55Z","timestamp":1788240415272,"version":"build-2803163510"},"reference-count":68,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"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":[[2021,12,1]]},"abstract":"<jats:p>\n                    Huntington's disease (HD) is one of the most common, dominantly inherited neurodegenerative disorders. It affects the striatum, cerebral cortex, and other subcortical structures leading to involuntary movement abnormalities, emotional disturbances, and cognitive impairments. HD is caused by a CAG\u2022CTG trinucleotide-repeat expansion in exon 1 of the\n                    <jats:italic toggle=\"yes\">huntingtin<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">HTT<\/jats:italic>\n                    ) gene leading to the formation of mutant HTT (mtHTT) protein aggregates. Besides the toxicity of the mutated protein, there is also evidence that mt\n                    <jats:italic toggle=\"yes\">HTT<\/jats:italic>\n                    transcripts contribute to the disease. Thus, the reduction of both mutated mRNA and protein would be most beneficial as a treatment. Previously, we designed a novel anti-gene oligonucleotide (AGO)-based strategy directly targeting the\n                    <jats:italic toggle=\"yes\">HTT<\/jats:italic>\n                    trinucleotide-repeats in DNA and reported downregulation of mRNA and protein in HD patient fibroblasts. In this study, we differentiate HD patient-derived induced pluripotent stem cells to investigate the efficacy of the AGO, a DNA\/Locked Nucleic Acid mixmer with phosphorothioate backbone, to modulate\n                    <jats:italic toggle=\"yes\">HTT<\/jats:italic>\n                    transcription during neural\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    development. For the first time, we demonstrate downregulation of\n                    <jats:italic toggle=\"yes\">HTT<\/jats:italic>\n                    mRNA following both naked and magnetofected delivery into neural stem cells (NSCs) and show that neither emergence of neural rosette structures nor self-renewal of NSCs is compromised. Furthermore, the inhibition potency of both\n                    <jats:italic toggle=\"yes\">HTT<\/jats:italic>\n                    mRNA and protein without off-target effects is confirmed in neurons. These results further validate an anti-gene approach for the treatment of HD.\n                  <\/jats:p>","DOI":"10.1089\/nat.2021.0021","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T12:20:26Z","timestamp":1631622026000},"page":"443-456","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Oligonucleotides Targeting DNA Repeats Downregulate\n                    <i>Huntingtin<\/i>\n                    Gene Expression in Huntington's Patient-Derived Neural Model System"],"prefix":"10.1177","volume":"31","author":[{"given":"Tea","family":"Umek","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Olsson","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden."},{"name":"Department of Clinical Pathology and Cytology, Sahlgrenska University Hospital, Gothenburg, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olof","family":"Gissberg","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama","family":"Saher","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden."},{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman M.","family":"Zaghloul","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden."},{"name":"Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin E.","family":"Lundin","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Clinical Research Center, Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper","family":"Wengel","sequence":"additional","affiliation":[{"name":"Department of Physics, Chemistry and Pharmacy, Biomolecular Nanoscale Engineering Center, University of Southern Denmark, Odense M, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Hanse","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden."},{"name":"Department of Neurodegenerative Disease, Institute of Neurology, University College London, London, United Kingdom."},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, M\u00f6lndal, Sweden."},{"name":"UK Dementia Research Institute at UCL, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dzeneta","family":"Vizlin-Hodzic","sequence":"additional","affiliation":[{"name":"Department of Physiology, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden."},{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. 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