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Featured by a distinctive propensity to form complex G-quadruplex structures, including large multimeric aggregates, the original 36-mer MS3 has been truncated to give a 33-mer (here named MS3-33) and a 17-mer (here named MS3-17). A combined use of different techniques (UV, CD, DSC, gel electrophoresis) allowed a detailed physicochemical characterization of these novel G-quadruplex-forming aptamers, tested in vitro on SH-SY5Y cells and in vivo on a Drosophila Huntington\u2019s disease model, in which these shorter MS3-derived oligonucleotides proved to have improved bioactivity in comparison with the parent aptamer.<\/jats:p>","DOI":"10.3390\/ijms232012412","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T21:11:51Z","timestamp":1666041111000},"page":"12412","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Truncated Analogues of a G-Quadruplex-Forming Aptamer Targeting Mutant Huntingtin: Shorter Is Better!"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7182-0757","authenticated-orcid":false,"given":"Claudia","family":"Riccardi","sequence":"first","affiliation":[{"name":"Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"D\u2019Aria","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominga","family":"Fasano","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, 2nd Division of Neurology, Center for Rare Diseases and InterUniversity Center for Research in Neurosciences, University of Campania Luigi Vanvitelli, 80131 Naples, Italy"},{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9342-3760","authenticated-orcid":false,"given":"Filomena Anna","family":"Digilio","sequence":"additional","affiliation":[{"name":"Research Institute on Terrestrial Ecosystems (IRET), UOS Naples-CNR, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Rosaria","family":"Carillo","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6096-3544","authenticated-orcid":false,"given":"Jussara","family":"Amato","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"De Rosa","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5332-6774","authenticated-orcid":false,"given":"Simona","family":"Paladino","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7213-9277","authenticated-orcid":false,"given":"Mariarosa Anna Beatrice","family":"Melone","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, 2nd Division of Neurology, Center for Rare Diseases and InterUniversity Center for Research in Neurosciences, University of Campania Luigi Vanvitelli, 80131 Naples, Italy"},{"name":"Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia, PA 19122-6078, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6295-6911","authenticated-orcid":false,"given":"Daniela","family":"Montesarchio","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Naples Federico II, 80126 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0360-6062","authenticated-orcid":false,"given":"Concetta","family":"Giancola","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.2174\/1389450053344975","article-title":"Huntington\u2019s disease: New frontiers for molecular and cell therapy","volume":"6","author":"Melone","year":"2005","journal-title":"Curr. 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