{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:48:52Z","timestamp":1792651732702,"version":"4.5.0"},"reference-count":166,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T00:00:00Z","timestamp":1660608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"German Ministry of Education and Research","doi-asserted-by":"publisher","award":["01ED16028"],"award-info":[{"award-number":["01ED16028"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Antisense oligonucleotides (ASOs) are single-stranded nucleic acid strings that can be used to selectively modify protein synthesis by binding complementary (pre-)mRNA sequences. By specific arrangements of DNA and RNA into a chain of nucleic acids and additional modifications of the backbone, sugar, and base, the specificity and functionality of the designed ASOs can be adjusted. Thereby cellular uptake, toxicity, and nuclease resistance, as well as binding affinity and specificity to its target (pre-)mRNA, can be modified. Several neurodegenerative diseases are caused by autosomal dominant toxic gain-of-function mutations, which lead to toxic protein products driving disease progression. ASOs targeting such mutations\u2014or even more comprehensively, associated variants, such as single nucleotide polymorphisms (SNPs)\u2014promise a selective degradation of the mutant (pre-)mRNA while sparing the wild type allele. By this approach, protein expression from the wild type strand is preserved, and side effects from an unselective knockdown of both alleles can be prevented. This makes allele-specific targeting strategies a focus for future personalized therapies. Here, we provide an overview of current strategies to develop personalized, allele-specific ASO therapies for the treatment of neurodegenerative diseases, such Huntington\u2019s disease (HD) and spinocerebellar ataxia type 3 (SCA3\/MJD).<\/jats:p>","DOI":"10.3390\/pharmaceutics14081708","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T03:15:27Z","timestamp":1660706127000},"page":"1708","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Towards Personalized Allele-Specific Antisense Oligonucleotide Therapies for Toxic Gain-of-Function Neurodegenerative Diseases"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0857-4266","authenticated-orcid":false,"given":"Jacob","family":"Helm","sequence":"first","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), 72076 T\u00fcbingen, Germany"},{"name":"Hertie Institute for Clinical Brain Research and Department of Neurology, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Graduate School of Cellular and Molecular Neuroscience, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludger","family":"Sch\u00f6ls","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), 72076 T\u00fcbingen, Germany"},{"name":"Hertie Institute for Clinical Brain Research and Department of Neurology, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1022-7482","authenticated-orcid":false,"given":"Stefan","family":"Hauser","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), 72076 T\u00fcbingen, Germany"},{"name":"Hertie Institute for Clinical Brain Research and Department of Neurology, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s13670-020-00341-7","article-title":"Antisense Oligonucleotide Therapeutics for Neurodegenerative Disorders","volume":"11","author":"Testa","year":"2022","journal-title":"Curr. 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