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AONs function at the cellular level by, for example, direct interference with the expression of gene products or the molecular activation of neuroprotective pathways. However, AON therapy faces a major obstacle limiting its clinical application for central nervous system (CNS) disorders: the blood\u2013brain barrier. Systemic administration of AONs leads to rapid clearance and breakdown of its molecules in the periphery. One way to overcome this obstacle is intracerebroventricular (ICV) delivery of the therapeutics directly to cerebrospinal fluid (CSF). Given the particular molecular structure of oligonucleotides, the (pharmaco) kinetic and distribution pattern of these compounds in the brain are yet to be clarified. In this study, 2\u2032OMePS oligonucleotide delivered through ICV into CSF reached the most key structures in the brain. The distribution of this oligonucleotide differed when comparing specific brain structures and cell groups. After 48\u2009h post-infusion, the distribution of the oligonucleotide reached its maximum and was found intracellularly in many key brain structures. These findings help understanding the kinetic and distribution pattern of 2\u2032OMePS oligonucleotide in the brain and will direct more rational and effective use of ICV drug delivery and unleash its full therapeutic potential in managing CNS diseases.<\/jats:p>","DOI":"10.1089\/nat.2016.0642","type":"journal-article","created":{"date-parts":[[2016,10,18]],"date-time":"2016-10-18T11:40:08Z","timestamp":1476790808000},"page":"4-10","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":14,"title":["Distribution and Penetration of Intracerebroventricularly Administered 2\u2032OMePS Oligonucleotide in the Mouse Brain"],"prefix":"10.1177","volume":"27","author":[{"given":"Jo\u00e3o","family":"Casaca-Carreira","sequence":"first","affiliation":[{"name":"Maastricht University Medical Center","place":["the Netherlands"]},{"name":"Maastricht University Medical Center","place":["the Netherlands"]},{"name":"European Graduate School of Neuroscience (EURON)","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasin","family":"Temel","sequence":"additional","affiliation":[{"name":"Maastricht University Medical Center","place":["the Netherlands"]},{"name":"Maastricht University Medical Center","place":["the Netherlands"]},{"name":"European Graduate School of Neuroscience (EURON)","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I\u00f1aki","family":"Larrakoetxea","sequence":"additional","affiliation":[{"name":"University of Girona","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Jahanshahi","sequence":"additional","affiliation":[{"name":"Maastricht University Medical Center","place":["the Netherlands"]},{"name":"Maastricht University Medical Center","place":["the Netherlands"]},{"name":"European Graduate School of Neuroscience (EURON)","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,10,18]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1089\/nat.2013.0452"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2016.3"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.05.009"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23717"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa073108"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1086-5802(16)30428-4"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60284-X"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2015.03.008"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.77"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70061-9"},{"key":"e_1_3_3_12_2","first-page":"347","article-title":"Antisense oligonucleotides: basic concepts and mechanisms","volume":"1","author":"Dias N","year":"2002","unstructured":"Dias N, and Stein CA. 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