{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:34:27Z","timestamp":1790534067100,"version":"4.1.0"},"reference-count":58,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,30]],"date-time":"2021-10-30T00:00:00Z","timestamp":1635552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"A G Leventis Foundation","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"European Commission Research Executive Agency","award":["Grant BIORISE No. 669026"],"award-info":[{"award-number":["Grant BIORISE No. 669026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Duchenne muscular dystrophy (DMD) is a fatal disorder characterised by progressive muscle wasting. It is caused by mutations in the dystrophin gene, which disrupt the open reading frame leading to the loss of functional dystrophin protein in muscle fibres. Antisense oligonucleotide (AON)-mediated skipping of the mutated exon, which allows production of a truncated but partially functional dystrophin protein, has been at the forefront of DMD therapeutic research for over two decades. Nonetheless, novel nucleic acid modifications and AON designs are continuously being developed to improve the clinical benefit profile of current drugs in the DMD pipeline. We herein designed a series of 15mer and 20mer AONs, consisting of 2\u2032O-Methyl (2\u2032OMe)- and locked nucleic acid (LNA)-modified nucleotides in different percentage compositions, and assessed their efficiency in inducing exon 23 skipping and dystrophin restoration in locally injected muscles of mdx mice. We demonstrate that LNA\/2\u2032OMe AONs with a 30% LNA composition were significantly more potent in inducing exon skipping and dystrophin restoration in treated mdx muscles, compared to a previously tested 2\u2032OMe AON and LNA\/2\u2032OMe chimeras with lower or higher LNA compositions. These results underscore the therapeutic potential of LNA\/2\u2032OMe AONs, paving the way for further experimentation to evaluate their benefit-toxicity profile following systemic delivery.<\/jats:p>","DOI":"10.3390\/ph14111113","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T22:24:22Z","timestamp":1635805462000},"page":"1113","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Intramuscular Evaluation of Chimeric Locked Nucleic Acid\/2\u2032OMethyl-Modified Antisense Oligonucleotides for Targeted Exon 23 Skipping in Mdx Mice"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5589-1697","authenticated-orcid":false,"given":"Michaella","family":"Georgiadou","sequence":"first","affiliation":[{"name":"Molecular Genetics, Function & Therapy Department, The Cyprus Institute of Neurology & Genetics, Nicosia 2371, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melina","family":"Christou","sequence":"additional","affiliation":[{"name":"Molecular Genetics, Function & Therapy Department, The Cyprus Institute of Neurology & Genetics, Nicosia 2371, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4232-122X","authenticated-orcid":false,"given":"Kleitos","family":"Sokratous","sequence":"additional","affiliation":[{"name":"Bioinformatics Group, The Cyprus Institute of Neurology & Genetics, Nicosia 2371, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9835-1009","authenticated-orcid":false,"given":"Jesper","family":"Wengel","sequence":"additional","affiliation":[{"name":"Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, DK-5230 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7065-1237","authenticated-orcid":false,"given":"Kyriaki","family":"Michailidou","sequence":"additional","affiliation":[{"name":"Biostatistics Unit, The Cyprus Institute of Neurology & Genetics, Nicosia 2371, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyriacos","family":"Kyriacou","sequence":"additional","affiliation":[{"name":"Cancer Genetics, Therapeutics & Ultrastructural Pathology Department, The Cyprus Institute of Neurology & Genetics, Nicosia 2371, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrie","family":"Koutsoulidou","sequence":"additional","affiliation":[{"name":"Molecular Genetics, Function & Therapy Department, The Cyprus Institute of Neurology & Genetics, Nicosia 2371, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos P.","family":"Mastroyiannopoulos","sequence":"additional","affiliation":[{"name":"Molecular Genetics, Function & Therapy Department, The Cyprus Institute of Neurology & Genetics, Nicosia 2371, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonidas A.","family":"Phylactou","sequence":"additional","affiliation":[{"name":"Molecular Genetics, Function & Therapy Department, The Cyprus Institute of Neurology & Genetics, Nicosia 2371, Cyprus"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/S1474-4422(03)00585-4","article-title":"Dystrophin and mutations: One gene, several proteins, multiple phenotypes","volume":"2","author":"Muntoni","year":"2003","journal-title":"Lancet. 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