{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:59:21Z","timestamp":1792454361334,"version":"4.5.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T00:00:00Z","timestamp":1639094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-14-CE13-0037-01"],"award-info":[{"award-number":["ANR-14-CE13-0037-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004794","name":"Centre National de la Recherche Scientifique","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004794","id-type":"DOI","asserted-by":"publisher"}]},{"name":"University Paris-Saclay, the Association Mon\u00e9gasque contre les Myopathies"},{"name":"Duchenne Parent project France"},{"DOI":"10.13039\/501100004792","name":"Minist\u00e8re de l'Enseignement Sup\u00e9rieur et de la Recherche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004792","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Paris Ile-de-France Region, the Fondation"},{"DOI":"10.13039\/501100002915","name":"Fondation pour la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["PLP20161036676"],"award-info":[{"award-number":["PLP20161036676"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Tricyclo-DNA (tcDNA) is a conformationally constrained oligonucleotide analog that has demonstrated great therapeutic potential as antisense oligonucleotide (ASO) for several diseases. Like most ASOs in clinical development, tcDNA were modified with phosphorothioate (PS) backbone for therapeutic purposes in order to improve their biodistribution by enhancing association with plasma and cell protein. Despite the advantageous protein binding properties, systemic delivery of PS-ASO remains limited and PS modifications can result in dose limiting toxicities in the clinic. Improving extra-hepatic delivery of ASO is highly desirable for the treatment of a variety of diseases including neuromuscular disorders such as Duchenne muscular dystrophy. We hypothesized that conjugation of palmitic acid to tcDNA could facilitate the delivery of the ASO from the bloodstream to the interstitium of the muscle tissues. We demonstrate here that palmitic acid conjugation enhances the potency of tcDNA-ASO in skeletal and cardiac muscles, leading to functional improvement in dystrophic mice with significantly reduced dose of administered ASO. Interestingly, palmitic acid-conjugated tcDNA with a full phosphodiester backbone proved effective with a particularly encouraging safety profile, offering new perspectives for the clinical development of PS-free tcDNA-ASO for neuromuscular diseases.<\/jats:p>","DOI":"10.1093\/nar\/gkab1199","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T15:13:58Z","timestamp":1638458038000},"page":"17-34","source":"Crossref","is-referenced-by-count":48,"title":["Palmitic acid conjugation enhances potency of tricyclo-DNA splice switching oligonucleotides"],"prefix":"10.1093","volume":"50","author":[{"given":"Karima","family":"Relizani","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris-Saclay , UVSQ, Inserm, END-ICAP, 78000 Versailles , France"},{"name":"SQY Therapeutics , UVSQ, 78180 Montigny le Bretonneux , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Echevarr\u00eda","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay , UVSQ, Inserm, END-ICAP, 78000 Versailles , France"},{"name":"SQY Therapeutics , UVSQ, 78180 Montigny le Bretonneux , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faouzi","family":"Zarrouki","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay , UVSQ, Inserm, END-ICAP, 78000 Versailles , France"},{"name":"Universit\u00e9 Paris-Saclay, CNRS, Institut des Neurosciences Paris Saclay , 91190, Gif-sur-Yvette , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Gastaldi","sequence":"additional","affiliation":[{"name":"LIA BAHN , centre scientifique de Monaco, 98000 , Monaco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe","family":"Dambrune","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay , UVSQ, Inserm, END-ICAP, 78000 Versailles , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippine","family":"Aupy","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay , UVSQ, Inserm, END-ICAP, 78000 Versailles , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Haeberli","sequence":"additional","affiliation":[{"name":"SYNTHENA AG , Bern , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Komisarski","sequence":"additional","affiliation":[{"name":"SYNTHENA AG , Bern , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Tensorer","sequence":"additional","affiliation":[{"name":"SQY Therapeutics , UVSQ, 78180 Montigny le Bretonneux , France"},{"name":"SYNTHENA AG , Bern , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibaut","family":"Larcher","sequence":"additional","affiliation":[{"name":"INRAE Oniris , UMR 703 PAnTher, Nantes , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fedor","family":"Svinartchouk","sequence":"additional","affiliation":[{"name":"SQY Therapeutics , UVSQ, 78180 Montigny le Bretonneux , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8783-8185","authenticated-orcid":false,"given":"Cyrille","family":"Vaillend","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay, CNRS, Institut des Neurosciences Paris Saclay , 91190, Gif-sur-Yvette , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Garcia","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay , UVSQ, Inserm, END-ICAP, 78000 Versailles , France"},{"name":"LIA BAHN , centre scientifique de Monaco, 98000 , Monaco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3938-1165","authenticated-orcid":false,"given":"Aur\u00e9lie","family":"Goyenvalle","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Saclay , UVSQ, Inserm, END-ICAP, 78000 Versailles , France"},{"name":"LIA BAHN , centre scientifique de Monaco, 98000 , Monaco"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,12,10]]},"reference":[{"key":"2023060913313960200_B1","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1016\/j.drudis.2018.08.004","article-title":"RNA-mediated therapies in myotonic dystrophy","volume":"23","author":"Overby","year":"2018","journal-title":"Drug Discov. 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Med."},{"key":"2023060913313960200_B7","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.omtn.2017.06.013","article-title":"Efficacy and safety profile of tricyclo-DNA antisense oligonucleotides in Duchenne muscular dystrophy mouse model","volume":"8","author":"Relizani","year":"2017","journal-title":"Mol Ther Nucleic Acids"},{"key":"2023060913313960200_B8","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.omtn.2017.02.009","article-title":"Efficient SMN rescue following subcutaneous tricyclo-DNA antisense oligonucleotide treatment","volume":"7","author":"Robin","year":"2017","journal-title":"Mol Ther Nucleic Acids"},{"key":"2023060913313960200_B9","doi-asserted-by":"crossref","first-page":"663","DOI":"10.2174\/1389450115666140321100304","article-title":"Phosphorothioate oligonucleotides: effectiveness and toxicity","volume":"15","author":"Iannitti","year":"2014","journal-title":"Curr. 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Mol. Genet."},{"key":"2023060913313960200_B30","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s10974-019-09535-9","article-title":"What is the level of dystrophin expression required for effective therapy of Duchenne muscular dystrophy","volume":"40","author":"Wells","year":"2019","journal-title":"J. Muscle Res. Cell Motil."},{"key":"2023060913313960200_B31","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1002\/ana.25951","article-title":"Very low residual dystrophin quantity is associated with milder dystrophinopathy","volume":"89","author":"de\u00a0Feraudy","year":"2021","journal-title":"Ann. 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