{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T12:59:17Z","timestamp":1780750757748,"version":"3.54.1"},"publisher-location":"New York, NY","reference-count":41,"publisher":"Springer US","isbn-type":[{"value":"9781071647295","type":"print"},{"value":"9781071647301","type":"electronic"}],"license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025]]},"DOI":"10.1007\/978-1-0716-4730-1_24","type":"book-chapter","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T12:59:52Z","timestamp":1753707592000},"page":"361-377","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optimization of 2\u2032,4\u2032-BNA\/LNA-Based Oligonucleotides for Splicing Modulation in Vitro"],"prefix":"10.1007","author":[{"given":"Takenori","family":"Shimo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Obika","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"issue":"18","key":"24_CR1","doi-asserted-by":"publisher","first-page":"8673","DOI":"10.1073\/pnas.90.18.8673","volume":"90","author":"Z Dominski","year":"1993","unstructured":"Dominski Z, Kole R (1993) Restoration of correct splicing in thalassemic pre-mRNA by antisense oligonucleotides. Proc Natl Acad Sci USA 90(18):8673\u20138677. https:\/\/doi.org\/10.1073\/pnas.90.18.8673","journal-title":"Proc Natl Acad Sci USA"},{"issue":"5","key":"24_CR2","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1016\/j.ymthe.2017.03.023","volume":"25","author":"CA Stein","year":"2017","unstructured":"Stein CA, Castanotto D (2017) FDA-approved oligonucleotide therapies in 2017. Mol Ther 25(5):1069\u20131075. https:\/\/doi.org\/10.1016\/j.ymthe.2017.03.023","journal-title":"Mol Ther"},{"issue":"3","key":"24_CR3","doi-asserted-by":"publisher","first-page":"339","DOI":"10.4155\/fmc.11.2","volume":"3","author":"T Yamamoto","year":"2011","unstructured":"Yamamoto T, Nakatani M, Narukawa K et al (2011) Antisense drug discovery and development. Future Med Chem 3(3):339\u2013365. https:\/\/doi.org\/10.4155\/fmc.11.2","journal-title":"Future Med Chem"},{"key":"24_CR4","doi-asserted-by":"publisher","first-page":"S71","DOI":"10.1016\/s0960-8966(02)00086-x","volume":"12","author":"A Aartsma-Rus","year":"2002","unstructured":"Aartsma-Rus A, Bremmer-Bout M, Janson AAM et al (2002) Targeted exon skipping as a potential gene correction therapy for Duchenne muscular dystrophy. Neuromuscul Disord 12:S71\u2013S77. https:\/\/doi.org\/10.1016\/s0960-8966(02)00086-x","journal-title":"Neuromuscul Disord"},{"issue":"8","key":"24_CR5","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1093\/hmg\/ddg100","volume":"12","author":"A Aartsma-Rus","year":"2003","unstructured":"Aartsma-Rus A, Janson AA, Kaman WE et al (2003) Therapeutic antisense-induced exon skipping in cultured muscle cells from six different DMD patients. Hum Mol Genet 12(8):907\u2013914. https:\/\/doi.org\/10.1093\/hmg\/ddg100","journal-title":"Hum Mol Genet"},{"issue":"12","key":"24_CR6","doi-asserted-by":"publisher","first-page":"8174","DOI":"10.1093\/nar\/gku512","volume":"42","author":"T Shimo","year":"2014","unstructured":"Shimo T, Tachibana K, Saito K et al (2014) Design and evaluation of locked nucleic acid-based splice-switching oligonucleotides in vitro. Nucleic Acids Res 42(12):8174\u20138187. https:\/\/doi.org\/10.1093\/nar\/gku512","journal-title":"Nucleic Acids Res"},{"issue":"4","key":"24_CR7","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1039\/c4md00468j","volume":"6","author":"Y Masaki","year":"2015","unstructured":"Masaki Y, Inde T, Nagata T et al (2015) Enhancement of exon skipping in mdx52 mice by 2\u2032-O-methyl-2-thioribothymidine incorporation into phosphorothioate oligonucleotides. Med Chem Commun 6(4):630\u2013633. https:\/\/doi.org\/10.1039\/c4md00468j","journal-title":"Med Chem Commun"},{"issue":"92","key":"24_CR8","doi-asserted-by":"publisher","first-page":"13467","DOI":"10.1039\/c6cc07447b","volume":"52","author":"BT Le","year":"2016","unstructured":"Le BT, Chen S, Abramov M et al (2016) Evaluation of anhydrohexitol nucleic acid, cyclohexenyl nucleic acid and d-altritol nucleic acid-modified 2\u2032-O-methyl RNA mixmer antisense oligonucleotides for exon skipping in vitro. Chem Commun (Camb) 52(92):13467\u201313470. https:\/\/doi.org\/10.1039\/c6cc07447b","journal-title":"Chem Commun (Camb)"},{"issue":"54","key":"24_CR9","doi-asserted-by":"publisher","first-page":"34049","DOI":"10.1039\/c7ra06091b","volume":"7","author":"BT Le","year":"2017","unstructured":"Le BT, Murayama K, Shabanpoor F et al (2017) Antisense oligonucleotide modified with serinol nucleic acid (SNA) induces exon skipping in mdx myotubes. RSC Adv 7(54):34049\u201334052. https:\/\/doi.org\/10.1039\/c7ra06091b","journal-title":"RSC Adv"},{"issue":"1","key":"24_CR10","doi-asserted-by":"publisher","first-page":"6078","DOI":"10.1038\/s41598-019-42523-0","volume":"9","author":"S Chen","year":"2019","unstructured":"Chen S, Le BT, Chakravarthy M et al (2019) Systematic evaluation of 2\u2032-fluoro modified chimeric antisense oligonucleotide-mediated exon skipping in vitro. Sci Rep 9(1):6078. https:\/\/doi.org\/10.1038\/s41598-019-42523-0","journal-title":"Sci Rep"},{"issue":"29","key":"24_CR11","doi-asserted-by":"publisher","first-page":"18035","DOI":"10.1021\/acsomega.0c01463","volume":"5","author":"BT Le","year":"2020","unstructured":"Le BT, Kosbar TR, Veedu RN (2020) Novel disulfide-bridged bioresponsive antisense oligonucleotide induces efficient splice modulation in muscle myotubes in vitro. ACS Omega 5(29):18035\u201318039. https:\/\/doi.org\/10.1021\/acsomega.0c01463","journal-title":"ACS Omega"},{"issue":"7","key":"24_CR12","doi-asserted-by":"publisher","first-page":"3526","DOI":"10.3390\/ijms22073526","volume":"22","author":"T Shimo","year":"2021","unstructured":"Shimo T, Nakatsuji Y, Tachibana K et al (2021) Design and in vitro evaluation of splice-switching oligonucleotides bearing locked nucleic acids, amido-bridged nucleic acids, and guanidine-bridged nucleic acids. Int J Mol Sci 22(7):3526. https:\/\/doi.org\/10.3390\/ijms22073526","journal-title":"Int J Mol Sci"},{"issue":"18","key":"24_CR13","doi-asserted-by":"publisher","first-page":"3790","DOI":"10.1039\/d2ob00304j","volume":"20","author":"Y Su","year":"2022","unstructured":"Su Y, Raguraman P, Veedu RN et al (2022) Phosphorothioate modification improves exon-skipping of antisense oligonucleotides based on sulfonyl phosphoramidates in mdx mouse myotubes. Org Biomol Chem 20(18):3790\u20133797. https:\/\/doi.org\/10.1039\/d2ob00304j","journal-title":"Org Biomol Chem"},{"issue":"3","key":"24_CR14","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1038\/mt.2008.205","volume":"17","author":"A Aartsma-Rus","year":"2009","unstructured":"Aartsma-Rus A, van Vliet L, Hirschi M et al (2009) Guidelines for antisense oligonucleotide design and insight into splice-modulating mechanisms. Mol Ther 17(3):548\u2013553. https:\/\/doi.org\/10.1038\/mt.2008.205","journal-title":"Mol Ther"},{"key":"24_CR15","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1007\/978-1-61779-767-5_9","volume":"867","author":"Y Takeshima","year":"2012","unstructured":"Takeshima Y, Yagi M, Matsuo M (2012) Optimizing RNA\/ENA chimeric antisense oligonucleotides using in vitro splicing. Methods Mol Biol 867:131\u2013141. https:\/\/doi.org\/10.1007\/978-1-61779-767-5_9","journal-title":"Methods Mol Biol"},{"key":"24_CR16","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/978-1-61779-767-5_10","volume":"867","author":"LJ Popplewell","year":"2012","unstructured":"Popplewell LJ, Malerba A, Dickson G (2012) Optimizing antisense oligonucleotides using phosphorodiamidate morpholino oligomers. Methods Mol Biol 867:143\u2013167. https:\/\/doi.org\/10.1007\/978-1-61779-767-5_10","journal-title":"Methods Mol Biol"},{"key":"24_CR17","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1007\/978-1-61779-767-5_11","volume":"867","author":"C Adkin","year":"2012","unstructured":"Adkin C, Fletcher S, Wilton SD (2012) Optimizing splice-switching oligomer sequences using 2\u2032-O-methyl phosphorothioate chemistry. Methods Mol Biol 867:169\u2013188. https:\/\/doi.org\/10.1007\/978-1-61779-767-5_11","journal-title":"Methods Mol Biol"},{"issue":"7","key":"24_CR18","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1089\/hum.2013.234","volume":"25","author":"P Disterer","year":"2014","unstructured":"Disterer P, Kryczka A, Liu Y et al (2014) Development of therapeutic splice-switching oligonucleotides. Hum Gene Ther 25(7):587\u2013598. https:\/\/doi.org\/10.1089\/hum.2013.234","journal-title":"Hum Gene Ther"},{"issue":"50","key":"24_CR19","doi-asserted-by":"publisher","first-page":"8735","DOI":"10.1016\/s0040-4039(97)10322-7","volume":"38","author":"S Obika","year":"1997","unstructured":"Obika S, Nanbu D, Hari Y et al (1997) Synthesis of 2\u2032-O,4\u2032-C-methyleneuridine and -cytidine. Novel bicyclic nucleosides having a fixed C3, -endo sugar puckering. Tetrahedron Lett 38(50):8735\u20138738. https:\/\/doi.org\/10.1016\/s0040-4039(97)10322-7","journal-title":"Tetrahedron Lett"},{"key":"24_CR20","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1039\/A708608C","volume":"1998","author":"SK Singh","year":"1998","unstructured":"Singh SK, Koshkin AA, Wengel J et al (1998) LNA (locked nucleic acids): synthesis and high-affinity nucleic acid recognition. Chem Commun (Camb) 1998:455\u2013456. https:\/\/doi.org\/10.1039\/A708608C","journal-title":"Chem Commun (Camb)"},{"issue":"10","key":"24_CR21","doi-asserted-by":"publisher","first-page":"5633","DOI":"10.1073\/pnas.97.10.5633","volume":"97","author":"C Wahlestedt","year":"2000","unstructured":"Wahlestedt C, Salmi P, Good L et al (2000) Potent and nontoxic antisense oligonucleotides containing locked nucleic acids. Proc Natl Acad Sci USA 97(10):5633\u20135638","journal-title":"Proc Natl Acad Sci USA"},{"issue":"19","key":"24_CR22","doi-asserted-by":"publisher","first-page":"5757","DOI":"10.1093\/nar\/gkh862","volume":"32","author":"KS Schmidt","year":"2004","unstructured":"Schmidt KS, Borkowski S, Kurreck J et al (2004) Application of locked nucleic acids to improve aptamer in vivo stability and targeting function. Nucleic Acids Res 32(19):5757\u20135765. https:\/\/doi.org\/10.1093\/nar\/gkh862","journal-title":"Nucleic Acids Res"},{"issue":"3","key":"24_CR23","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.ddtec.2005.08.012","volume":"2","author":"S Kauppinen","year":"2005","unstructured":"Kauppinen S, Vester B, Wengel J (2005) Locked nucleic acid (LNA): high affinity targeting of RNA for diagnostics and therapeutics. Drug Discov Today Technol 2(3):287\u2013290. https:\/\/doi.org\/10.1016\/j.ddtec.2005.08.012","journal-title":"Drug Discov Today Technol"},{"issue":"3","key":"24_CR24","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1158\/1535-7163.MCT-06-0195","volume":"6","author":"OR Mook","year":"2007","unstructured":"Mook OR, Baas F, de Wissel MB et al (2007) Evaluation of locked nucleic acid-modified small interfering RNA in vitro and in vivo. Mol Cancer Ther 6(3):833\u2013843. https:\/\/doi.org\/10.1158\/1535-7163.MCT-06-0195","journal-title":"Mol Cancer Ther"},{"issue":"8","key":"24_CR25","doi-asserted-by":"publisher","first-page":"1678","DOI":"10.1182\/blood-2012-02-410647","volume":"120","author":"Y Zhang","year":"2012","unstructured":"Zhang Y, Roccaro AM, Rombaoa C et al (2012) LNA-mediated anti-miR-155 silencing in low-grade B-cell lymphomas. Blood 120(8):1678\u20131686. https:\/\/doi.org\/10.1182\/blood-2012-02-410647","journal-title":"Blood"},{"key":"24_CR26","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.ejphar.2013.11.004","volume":"723","author":"T Yamamoto","year":"2014","unstructured":"Yamamoto T, Obika S, Nakatani M et al (2014) Locked nucleic acid antisense inhibitor targeting apolipoprotein C-III efficiently and preferentially removes triglyceride from large very low-density lipoprotein particles in murine plasma. Eur J Pharmacol 723:353\u2013359. https:\/\/doi.org\/10.1016\/j.ejphar.2013.11.004","journal-title":"Eur J Pharmacol"},{"issue":"1","key":"24_CR27","doi-asserted-by":"publisher","first-page":"3672","DOI":"10.1038\/s41598-017-03850-2","volume":"7","author":"A Touznik","year":"2017","unstructured":"Touznik A, Maruyama R, Hosoki K et al (2017) LNA\/DNA mixmer-based antisense oligonucleotides correct alternative splicing of the SMN2 gene and restore SMN protein expression in type 1 SMA fibroblasts. Sci Rep 7(1):3672. https:\/\/doi.org\/10.1038\/s41598-017-03850-2","journal-title":"Sci Rep"},{"issue":"4","key":"24_CR28","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1016\/j.ymthe.2006.05.017","volume":"14","author":"J Roberts","year":"2006","unstructured":"Roberts J, Palma E, Sazani P et al (2006) Efficient and persistent splice switching by systemically delivered LNA oligonucleotides in mice. Mol Ther 14(4):471\u2013475. https:\/\/doi.org\/10.1016\/j.ymthe.2006.05.017","journal-title":"Mol Ther"},{"issue":"1","key":"24_CR29","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1089\/nat.2013.0454","volume":"24","author":"P Jarver","year":"2014","unstructured":"Jarver P, O\u2019Donovan L, Gait MJ (2014) A chemical view of oligonucleotides for exon skipping and related drug applications. Nucleic Acid Ther 24(1):37\u201347. https:\/\/doi.org\/10.1089\/nat.2013.0454","journal-title":"Nucleic Acid Ther"},{"issue":"2","key":"24_CR30","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1042\/BJ20080013","volume":"412","author":"P Guterstam","year":"2008","unstructured":"Guterstam P, Lindgren M, Johansson H et al (2008) Splice-switching efficiency and specificity for oligonucleotides with locked nucleic acid monomers. Biochem J 412(2):307\u2013313. https:\/\/doi.org\/10.1042\/BJ20080013","journal-title":"Biochem J"},{"key":"24_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/mtna.2012.58","volume":"2","author":"AS Yilmaz-Elis","year":"2013","unstructured":"Yilmaz-Elis AS, Aartsma-Rus A, \u2018t Hoen PA et al (2013) Inhibition of IL-1 signaling by antisense oligonucleotide-mediated exon skipping of IL-1 receptor accessory protein (IL-1RAcP). Mol Ther Nucleic Acids 2:e66. https:\/\/doi.org\/10.1038\/mtna.2012.58","journal-title":"Mol Ther Nucleic Acids"},{"key":"24_CR32","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.omtn.2017.09.002","volume":"9","author":"BT Le","year":"2017","unstructured":"Le BT, Adams AM, Fletcher S et al (2017) Rational design of short locked nucleic acid-modified 2\u2032-O-methyl antisense oligonucleotides for efficient exon-skipping in vitro. Mol Ther Nucleic Acids 9:155\u2013161. https:\/\/doi.org\/10.1016\/j.omtn.2017.09.002","journal-title":"Mol Ther Nucleic Acids"},{"issue":"1","key":"24_CR33","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gnh015","volume":"32","author":"MJ Cavaluzzi","year":"2004","unstructured":"Cavaluzzi MJ, Borer PN (2004) Revised UV extinction coefficients for nucleoside-5\u2032-monophosphates and unpaired DNA and RNA. Nucleic Acids Res 32(1):e13. https:\/\/doi.org\/10.1093\/nar\/gnh015","journal-title":"Nucleic Acids Res"},{"issue":"13","key":"24_CR34","doi-asserted-by":"publisher","first-page":"6421","DOI":"10.1093\/nar\/gkt360","volume":"41","author":"S Liu","year":"2013","unstructured":"Liu S, Wang J, Su Y et al (2013) Quantitative assessment of Tet-induced oxidation products of 5-methylcytosine in cellular and tissue DNA. Nucleic Acids Res 41(13):6421\u20136429. https:\/\/doi.org\/10.1093\/nar\/gkt360","journal-title":"Nucleic Acids Res"},{"issue":"12","key":"24_CR35","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1038\/gt.2011.100","volume":"18","author":"KA Lennox","year":"2011","unstructured":"Lennox KA, Behlke MA (2011) Chemical modification and design of anti-miRNA oligonucleotides. Gene Ther 18(12):1111\u20131120. https:\/\/doi.org\/10.1038\/gt.2011.100","journal-title":"Gene Ther"},{"issue":"48","key":"24_CR36","doi-asserted-by":"publisher","first-page":"6850","DOI":"10.1039\/c8cc09648a","volume":"55","author":"T Shimo","year":"2019","unstructured":"Shimo T, Tachibana K, Kawawaki Y et al (2019) Enhancement of exon skipping activity by reduction in the secondary structure content of LNA-based splice-switching oligonucleotides. Chem Commun (Camb) 55(48):6850\u20136853. https:\/\/doi.org\/10.1039\/c8cc09648a","journal-title":"Chem Commun (Camb)"},{"issue":"3","key":"24_CR37","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0120058","volume":"10","author":"Y Echigoya","year":"2015","unstructured":"Echigoya Y, Mouly V, Garcia L et al (2015) In silico screening based on predictive algorithms as a design tool for exon skipping oligonucleotides in Duchenne muscular dystrophy. PLoS One 10(3):e0120058. https:\/\/doi.org\/10.1371\/journal.pone.0120058","journal-title":"PLoS One"},{"key":"24_CR38","doi-asserted-by":"publisher","unstructured":"Echigoya Y, Lim KRQ, Trieu N et al (2017) Quantitative antisense screening and optimization for exon 51 skipping in Duchenne muscular dystrophy. Mol Ther. https:\/\/doi.org\/10.1016\/j.ymthe.2017.07.014","DOI":"10.1016\/j.ymthe.2017.07.014"},{"issue":"24","key":"24_CR39","doi-asserted-by":"publisher","first-page":"1793","DOI":"10.1016\/0024-3205(91)90480-Y","volume":"49","author":"S Akhtar","year":"1991","unstructured":"Akhtar S, Kole R, Juliano RL (1991) Stability of antisense DNA oligodeoxynucleotide analogs in cellular extracts and sera. Life Sci 49(24):1793\u20131801","journal-title":"Life Sci"},{"issue":"9","key":"24_CR40","doi-asserted-by":"publisher","first-page":"1911","DOI":"10.1093\/nar\/30.9.1911","volume":"30","author":"J Kurreck","year":"2002","unstructured":"Kurreck J, Wyszko E, Gillen C et al (2002) Design of antisense oligonucleotides stabilized by locked nucleic acids. Nucleic Acids Res 30(9):1911\u20131918","journal-title":"Nucleic Acids Res"},{"issue":"9","key":"24_CR41","doi-asserted-by":"publisher","first-page":"2764","DOI":"10.1073\/pnas.1415525112","volume":"112","author":"M Yoshida","year":"2015","unstructured":"Yoshida M, Kataoka N, Miyauchi K et al (2015) Rectifier of aberrant mRNA splicing recovers tRNA modification in familial dysautonomia. Proc Natl Acad Sci USA 112(9):2764\u20132769. https:\/\/doi.org\/10.1073\/pnas.1415525112","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["Methods in Molecular Biology","Exon Skipping and Inclusion Therapies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/978-1-0716-4730-1_24","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T12:05:41Z","timestamp":1780747541000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/978-1-0716-4730-1_24"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"ISBN":["9781071647295","9781071647301"],"references-count":41,"URL":"https:\/\/doi.org\/10.1007\/978-1-0716-4730-1_24","relation":{},"ISSN":["1064-3745","1940-6029"],"issn-type":[{"value":"1064-3745","type":"print"},{"value":"1940-6029","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025]]},"assertion":[{"value":"29 July 2025","order":1,"name":"first_online","label":"First Online","group":{"name":"ChapterHistory","label":"Chapter History"}}]}}