{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:39:22Z","timestamp":1760236762279,"version":"build-2065373602"},"reference-count":48,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,17]],"date-time":"2021-12-17T00:00:00Z","timestamp":1639699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Steric blocking antisense oligonucleotides (ASO) are promising tools for splice modulation such as exon-skipping, although their therapeutic effect may be compromised by insufficient delivery. To address this issue, we investigated the synthesis of a 20-mer 2\u2032-OMe PS oligonucleotide conjugated at 3\u2032-end with ursodeoxycholic acid (UDCA) involved in the targeting of human DMD exon 51, by exploiting both a pre-synthetic and a solution phase approach. The two approaches have been compared. Both strategies successfully provided the desired ASO 51 3\u2032-UDC in good yield and purity. It should be pointed out that the pre-synthetic approach insured better yields and proved to be more cost-effective. The exon skipping efficiency of the conjugated oligonucleotide was evaluated in myogenic cell lines and compared to that of unconjugated one: a better performance was determined for ASO 51 3\u2032-UDC with an average 9.5-fold increase with respect to ASO 51.<\/jats:p>","DOI":"10.3390\/molecules26247662","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T02:50:18Z","timestamp":1639968618000},"page":"7662","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Synthesis and Exon-Skipping Properties of a 3\u2032-Ursodeoxycholic Acid-Conjugated Oligonucleotide Targeting DMD Pre-mRNA: Pre-Synthetic versus Post-Synthetic Approach"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5402-4732","authenticated-orcid":false,"given":"Elena","family":"Marchesi","sequence":"first","affiliation":[{"name":"Department of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9937-009X","authenticated-orcid":false,"given":"Matteo","family":"Bovolenta","sequence":"additional","affiliation":[{"name":"Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Preti","sequence":"additional","affiliation":[{"name":"Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4237-1198","authenticated-orcid":false,"given":"Massimo L.","family":"Capobianco","sequence":"additional","affiliation":[{"name":"Institute of Organic Synthesis and Photoreactivity, Italian National Research Council, 40129 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamel","family":"Mamchaoui","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Myologie, Institut de Myologie, Sorbonne Universit\u00e9, Inserm, F-75013 Paris, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8221-2095","authenticated-orcid":false,"given":"Monica","family":"Bertoldo","sequence":"additional","affiliation":[{"name":"Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Institute of Organic Synthesis and Photoreactivity, Italian National Research Council, 40129 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5189-011X","authenticated-orcid":false,"given":"Daniela","family":"Perrone","sequence":"additional","affiliation":[{"name":"Department of Environmental and Prevention Sciences, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3705","DOI":"10.2147\/DDDT.S179008","article-title":"Saponins enhance exon skipping of 2\u2019-O-methyl phosphorothioate oligonucleotide in vitro and in vivo","volume":"12","author":"Wang","year":"2018","journal-title":"Drug Des. 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