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In particular, the efficacy of antisense therapy for suppression of normal, pathogenic, or cryptic splice sites has been demonstrated in cellular and animal models and has already reached the clinical trials phase for Duchenne muscular dystrophy. In different inherited metabolic diseases, splice switching oligonucleotides (SSOs) have been used with success in patients' cells to force pseudoexon skipping or to block cryptic splice sites, in both cases recovering normal transcript and protein and correcting the enzyme deficiency. However, future\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    studies require individual approaches for delivery depending on the gene defect involved, given the different patterns of tissue and organ expression. Herein we review the state of the art of antisense therapy targeting RNA splicing in metabolic diseases, grouped according to their expression patterns\u2014multisystemic, hepatic, or in central nervous system (CNS)\u2014and summarize the recent progress achieved in the field of\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    delivery of oligonucleotides to each organ or system. Successful body-wide distribution of SSOs and preferential distribution in the liver after systemic administration have been reported in murine models for different diseases, while for CNS limited data are available, although promising results with intratechal injections have been achieved.\n                  <\/jats:p>","DOI":"10.1089\/nat.2013.0453","type":"journal-article","created":{"date-parts":[[2014,2,7]],"date-time":"2014-02-07T15:20:37Z","timestamp":1391786437000},"page":"48-56","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":13,"title":["Antisense Mediated Splicing Modulation For Inherited Metabolic Diseases: Challenges for Delivery"],"prefix":"10.1177","volume":"24","author":[{"given":"Belen","family":"P\u00e9rez","sequence":"first","affiliation":[{"name":"Universidad Aut\u00f3noma de Madrid","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lluisa","family":"Vilageliu","sequence":"additional","affiliation":[{"name":"Universitat de Barcelona","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Grinberg","sequence":"additional","affiliation":[{"name":"Universitat de Barcelona","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lourdes R.","family":"Desviat","sequence":"additional","affiliation":[{"name":"Universidad Aut\u00f3noma de Madrid","place":["Spain"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2014,2,7]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/156652312800840621"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60961-0"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21529"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0609com"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-12-474585"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60756-3"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-004-1377-8"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-006-0068-3"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2009.07520.x"},{"key":"e_1_3_3_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.257"},{"key":"e_1_3_3_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2013.04.005"},{"key":"e_1_3_3_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr217"},{"key":"e_1_3_3_14_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200140020-00003"},{"key":"e_1_3_3_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2008.03.009"},{"key":"e_1_3_3_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000086427"},{"key":"e_1_3_3_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.04.004"},{"key":"e_1_3_3_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.11.017"},{"key":"e_1_3_3_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.05.002"},{"key":"e_1_3_3_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R112.429274"},{"key":"e_1_3_3_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31735"},{"key":"e_1_3_3_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1011367"},{"key":"e_1_3_3_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21290"},{"key":"e_1_3_3_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.05.013"},{"key":"e_1_3_3_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.11.4142"},{"key":"e_1_3_3_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10485"},{"key":"e_1_3_3_27_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005331523477"},{"key":"e_1_3_3_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.2000.89.1.81"},{"key":"e_1_3_3_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70211-X"},{"key":"e_1_3_3_30_1","first-page":"125","article-title":"RNA therapeutics: beyond RNA interference and antisense oligonucleotides","volume":"11","author":"KOLE R.","year":"2012","unstructured":"KOLE R., , KRAINER A.R., , and ALTMAN S. 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