{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:49:58Z","timestamp":1792043398239,"version":"4.4.0"},"reference-count":25,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"publisher","award":["MR\/W029324\/1"],"award-info":[{"award-number":["MR\/W029324\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"publisher","award":["MR\/Z000025\/1"],"award-info":[{"award-number":["MR\/Z000025\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"UK Medical Research Council","doi-asserted-by":"publisher","award":["MC\/PC\/20061"],"award-info":[{"award-number":["MC\/PC\/20061"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2026,9,28]]},"abstract":"<jats:p>\n                    Gapmer antisense oligonucleotides (ASOs) represent a clinically validated therapeutic platform, with a 2\u2032\u2010\n                    <jats:italic>O<\/jats:italic>\n                    \u2010methoxyethyl modification commonplace within the flanking regions. An alternative sugar modification, incorporation of 4\u2032\u2010thioribose, has demonstrated enhanced nuclease resistance in siRNAs and aptamers, but incorporation of this motif into gapmer architectures remains underexplored. Herein, we report the synthesis of a 4\u2032\u2010thiouridine phosphoramidite building block and its incorporation into gapmer ASOs targeting\n                    <jats:italic>PTEN<\/jats:italic>\n                    . Evaluation of sequences containing 4\u2032\u2010thiouridine in the flanking regions (compared with 2\u2032\u2010\n                    <jats:italic>O<\/jats:italic>\n                    \u2010methoxyethyl) and varying phosphorothioate linkage composition demonstrates that the modified gapmers maintain equivalent knockdown efficacy under transfection and gymnotic delivery. These findings indicate 4\u2032\u2010thioribose as an alternative sugar modification for wider exploration within gapmer ASOs.\n                  <\/jats:p>","DOI":"10.1002\/cbic.70533","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T19:29:01Z","timestamp":1790537341000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A 4\u2032\u2010Thioribouridine Modification Mimics 2\u2032\u2010\n                    <i>O<\/i>\n                    \u2010Methoxyethyl in ASO\u2010Like 20\u2010Mers Targeting\n                    <i>PTEN<\/i>\n                    Knockdown"],"prefix":"10.1002","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4007-240X","authenticated-orcid":false,"given":"Joanna E.","family":"Parkes","sequence":"first","affiliation":[{"name":"MRC Nucleic Acid Therapy Accelerator (NATA) Research Complex at Harwell (RCaH)  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caecilie M. M.","family":"Benckendorff","sequence":"additional","affiliation":[{"name":"Manchester Institute of Biotechnology &amp; Department of Chemistry University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna L.","family":"Malinowska","sequence":"additional","affiliation":[{"name":"MRC Nucleic Acid Therapy Accelerator (NATA) Research Complex at Harwell (RCaH)  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Roberts","sequence":"additional","affiliation":[{"name":"Manchester Institute of Biotechnology &amp; Department of Chemistry University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harley L.","family":"Huynh","sequence":"additional","affiliation":[{"name":"MRC Nucleic Acid Therapy Accelerator (NATA) Research Complex at Harwell (RCaH)  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9007-4964","authenticated-orcid":false,"given":"Sritama","family":"Bose","sequence":"additional","affiliation":[{"name":"MRC Nucleic Acid Therapy Accelerator (NATA) Research Complex at Harwell (RCaH)  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lo\u00efc M.","family":"Cochard","sequence":"additional","affiliation":[{"name":"MRC Nucleic Acid Therapy Accelerator (NATA) Research Complex at Harwell (RCaH)  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aisling N\u00ed","family":"Cheallaigh","sequence":"additional","affiliation":[{"name":"Manchester Institute of Biotechnology &amp; Department of Chemistry University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4584-3189","authenticated-orcid":false,"given":"Sarah L.","family":"Lovelock","sequence":"additional","affiliation":[{"name":"Manchester Institute of Biotechnology &amp; Department of Chemistry University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3347-2461","authenticated-orcid":false,"given":"Peter L.","family":"Oliver","sequence":"additional","affiliation":[{"name":"MRC Nucleic Acid Therapy Accelerator (NATA) Research Complex at Harwell (RCaH)  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6533-3306","authenticated-orcid":false,"given":"Gavin J.","family":"Miller","sequence":"additional","affiliation":[{"name":"Manchester Institute of Biotechnology &amp; Department of Chemistry University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3765"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565\u2010021\u201000898\u20100"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14020260"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad067"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xphs.2024.04.021"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010021\u201000162\u2010z"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3802"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099\u20101352(200001\/02)13:1<44::AID\u2010JMR486>3.0.CO;2\u20106"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hlca.202200169"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.6.1272"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1089\/nat.2014.0506"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.1c01306"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn1088"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki704"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki578"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/21.7.1587"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/15257779508012526"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh705"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aed6880"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm050822c"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.878"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1039\/d1ob02097h"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2022.128605"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202405040"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.4c02409"}],"container-title":["ChemBioChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbic.70533","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbic.70533","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbic.70533","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:43:47Z","timestamp":1792043027000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cbic.70533"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,27]]},"references-count":25,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2026,9,28]]}},"alternative-id":["10.1002\/cbic.70533"],"URL":"https:\/\/doi.org\/10.1002\/cbic.70533","archive":["Portico"],"relation":{},"ISSN":["1439-4227","1439-7633"],"issn-type":[{"value":"1439-4227","type":"print"},{"value":"1439-7633","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,27]]},"assertion":[{"value":"2026-03-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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