{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T07:00:59Z","timestamp":1780383659642,"version":"3.54.1"},"reference-count":24,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Nucleic Acid Therapeutics"],"published-print":{"date-parts":[[2021,6,1]]},"abstract":"<jats:p>\n                    Antisense-mediated exon skipping constitutes a promising new modality for treatment of Duchenne Muscular Dystrophy (DMD), which is caused by gene mutations that typically introduce a translation stop codon in the dystrophin gene, thereby abolishing production of functional dystrophin protein. The exon removal can restore translation to produce a shortened, but still partially functional dystrophin protein. Peptide nucleic acid (PNA) as a potential antisense drug has previously been shown to restore the expression of functional dystrophin by splice modulation in the mdx mouse model of DMD. In this study, we compare systemic administration of a 20-mer splice switching antisense PNA oligomer through intravenous (i.v.) and subcutaneous (s.c.) routes in the mdx mice. Furthermore, the effect of\n                    <jats:italic toggle=\"yes\">in situ<\/jats:italic>\n                    forming depot technology (BEPO\n                    <jats:sup>\u00ae<\/jats:sup>\n                    ) and PNA-oligonucleotide formulation was studied.\n                    <jats:italic toggle=\"yes\">In vivo<\/jats:italic>\n                    fluorescence imaging analysis showed fast renal\/bladder excretion of the PNA (t\n                    <jats:sub>\u00bd<\/jats:sub>\n                    \u223c 20\u2009min) for i.v. administration, while s.c. administration showed a two to three times slower excretion. The release from the BEPO depot exhibited biphasic kinetics with a slow release (t\n                    <jats:sub>\u00bd<\/jats:sub>\n                    \u223c 10 days) of 50% of the dose. In all cases, some accumulation in kidneys and liver could be detected. Formulation of PNA as a duplex hybridization complex with a complementary phosphorothioate oligonucleotide increased the solubility of the PNA. However, none of these alternative administration methods resulted in significantly improved antisense activity. Therefore, either more sophisticated formulations such as designed nanoparticles or conjugation to delivery ligands must be utilized to improve both pharmacokinetics as well as tissue targeting and availability. On the other hand, the results show that s.c. and BEPO depot administration of PNA are feasible and allow easier, higher, and less frequent dosing, as well as more controlled release, which can be exploited both for animal model studies as well as eventually in the clinic in terms of dosing optimization.\n                  <\/jats:p>","DOI":"10.1089\/nat.2020.0856","type":"journal-article","created":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T17:38:25Z","timestamp":1595007505000},"page":"208-219","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["Approaches for Systemic Delivery of Dystrophin Antisense Peptide Nucleic Acid in the mdx Mouse Model"],"prefix":"10.1177","volume":"31","author":[{"given":"Camilla","family":"Brolin","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernest Wee Kiat","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvestre","family":"Grizot","sequence":"additional","affiliation":[{"name":"MedinCell, Jacou, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline Holkmann","family":"Olsen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Rigshospitalet, Copenhagen, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niloofar","family":"Yavari","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas O.","family":"Krag","sequence":"additional","affiliation":[{"name":"Department of Neurology, Copenhagen Neuromuscular Center, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter E.","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,6,4]]},"reference":[{"key":"e_1_3_4_2_2","first-page":"583","article-title":"Therapeutic peptide nucleic acids: principles, limitations, and opportunities","volume":"90","author":"Quijano E","year":"2017","unstructured":"Quijano E, , Bahal R, , Ricciardi A, , Saltzman WM, and Glazer PM. (2017). Therapeutic peptide nucleic acids: principles, limitations, and opportunities. 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