{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T19:47:05Z","timestamp":1785008825702,"version":"3.55.0"},"reference-count":107,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Survivin (BIRC5) is a key inhibitor of apoptosis that is highly overexpressed in many cancers, where it promotes tumour cell survival, mitotic progression, and resistance to therapy. Because survivin is largely absent from normal adult tissues, it represents a selective and promising target for cancer treatment. Antisense oligonucleotides (ASOs) provide a precise approach to silence survivin by targeting its transcripts. Preclinical studies have shown that ASO-mediated reduction of survivin is associated with increased cancer cell death, inhibition of tumour growth, and enhanced sensitivity to other treatments. Early-phase clinical trials of survivin-targeting ASOs have shown evidence of target engagement but ultimately failed to demonstrate consistent clinical benefit and\/or encountered dose-limiting toxicities, which hindered their further development. This review outlines survivin\u2019s central role in cancer biology, the principles of ASO therapeutics (sequence design, mechanisms of action, chemical modifications, and delivery strategies), and the progress in preclinical and clinical development of survivin-targeting ASOs, while also discussing key challenges that may contribute to their clinical limitations, including inefficient delivery, off-target effects, and systemic toxicities. Collectively, the current status of survivin-targeting ASOs underscores the need for synergistic optimization of delivery platforms and molecular chemistry to improve efficacy and safety, thereby enabling their use in personalised and combination cancer treatment approaches.<\/jats:p>","DOI":"10.3390\/molecules31132283","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T08:26:15Z","timestamp":1782807975000},"page":"2283","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Survivin-Targeting Antisense Oligonucleotides in Cancer Therapy"],"prefix":"10.3390","volume":"31","author":[{"given":"Bal Hari","family":"Poudel","sequence":"first","affiliation":[{"name":"Personalised Medicine Centre, Health Futures Institute, Murdoch University, Murdoch, WA 6150, Australia"},{"name":"Precision Nucleic Acid Therapeutics, Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, Australia"},{"name":"ProGenis Pharmaceuticals Pty Ltd., Bentley, WA 6102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6878-9587","authenticated-orcid":false,"given":"Suxiang","family":"Chen","sequence":"additional","affiliation":[{"name":"Personalised Medicine Centre, Health Futures Institute, Murdoch University, Murdoch, WA 6150, Australia"},{"name":"Precision Nucleic Acid Therapeutics, Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh N.","family":"Veedu","sequence":"additional","affiliation":[{"name":"Personalised Medicine Centre, Health Futures Institute, Murdoch University, Murdoch, WA 6150, Australia"},{"name":"Precision Nucleic Acid Therapeutics, Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, Australia"},{"name":"ProGenis Pharmaceuticals Pty Ltd., Bentley, WA 6102, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8581","DOI":"10.1038\/sj.onc.1207113","article-title":"Survivin, versatile modulation of cell division and apoptosis in cancer","volume":"22","author":"Altieri","year":"2003","journal-title":"Oncogene"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"jcs223826","DOI":"10.1242\/jcs.223826","article-title":"Survivin at a glance","volume":"132","author":"Wheatley","year":"2019","journal-title":"J. Cell Sci."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Raguraman, P., Balachandran, A.A., Chen, S., Diermeier, S.D., and Veedu, R.N. (2021). Antisense oligonucleotide-mediated splice switching: Potential therapeutic approach for cancer mitigation. Cancers, 13.","DOI":"10.3390\/cancers13215555"},{"key":"ref_5","first-page":"347","article-title":"Antisense oligonucleotides: Basic concepts and mechanisms","volume":"1","author":"Dias","year":"2002","journal-title":"Mol. Cancer Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1007\/s40259-024-00644-7","article-title":"Splice-modulating antisense oligonucleotides as therapeutics for inherited metabolic diseases","volume":"38","author":"Chen","year":"2024","journal-title":"BioDrugs"},{"key":"ref_7","first-page":"3143","article-title":"The cancer antiapoptosis mouse survivin gene: Characterization of locus and transcriptional requirements of basal and cell cycle-dependent expression","volume":"59","author":"Li","year":"1999","journal-title":"Cancer Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"314","DOI":"10.7150\/jca.13332","article-title":"Survivin and tumorigenesis: Molecular mechanisms and therapeutic strategies","volume":"7","author":"Chen","year":"2016","journal-title":"J. Cancer"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1038\/77929","article-title":"Structure of the human anti-apoptotic protein survivin reveals a dimeric arrangement","volume":"7","author":"Verdecia","year":"2000","journal-title":"Nat. Struct. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2007.07.045","article-title":"Structure of a Survivin-Borealin-INCENP core complex reveals how chromosomal passengers travel together","volume":"131","author":"Jeyaprakash","year":"2007","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1126\/science.1189505","article-title":"Survivin reads phosphorylated histone H3 threonine 3 to activate the mitotic kinase Aurora B","volume":"330","author":"Kelly","year":"2010","journal-title":"Science"},{"key":"ref_12","first-page":"6097","article-title":"Survivin-\u0394Ex3 and survivin-2B: Two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties","volume":"59","author":"Mahotka","year":"1999","journal-title":"Cancer Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1476-4598-4-11","article-title":"Survivin 2\u03b1: A novel survivin splice variant expressed in human malignancies","volume":"4","author":"Caldas","year":"2005","journal-title":"Mol. Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1002\/ijc.21995","article-title":"In vivo expression of survivin and its splice variant survivin-2B: Impact on clinical outcome in acute myeloid leukemia","volume":"119","author":"Wagner","year":"2006","journal-title":"Int. J. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/sj.bjc.6602314","article-title":"Expression of survivin and its splice variants survivin-2B and survivin-\u0394Ex3 in breast cancer","volume":"92","author":"Ryan","year":"2005","journal-title":"Br. J. Cancer"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1373\/clinchem.2006.071613","article-title":"Do the survivin (BIRC5) splice variants modulate or add to the prognostic value of total survivin in breast cancer?","volume":"52","author":"Span","year":"2006","journal-title":"Clin. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1002\/pbc.24822","article-title":"BIRC5 (survivin) splice variant expression correlates with refractory disease and poor outcome in pediatric acute myeloid leukemia: A report from the Children\u2019s Oncology Group","volume":"61","author":"Moore","year":"2014","journal-title":"Pediatr. Blood Cancer"},{"key":"ref_18","first-page":"230","article-title":"Suppression of survivin phosphorylation on Thr34 by flavopiridol enhances tumor cell apoptosis","volume":"63","author":"Wall","year":"2003","journal-title":"Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.4161\/cc.6.10.4179","article-title":"Phosphorylation by Aurora-B negatively regulates survivin function during mitosis","volume":"6","author":"Wheatley","year":"2007","journal-title":"Cell Cycle"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"36129","DOI":"10.1074\/jbc.M110.152777","article-title":"Acetylation directs survivin nuclear localization to repress STAT3 oncogenic activity","volume":"285","author":"Wang","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.bbrc.2021.08.050","article-title":"Regulation of survivin protein stability by USP35 is evolutionarily conserved","volume":"574","author":"Wang","year":"2021","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1006\/excr.2002.5492","article-title":"CRM1-mediated nuclear export determines the cytoplasmic localization of the antiapoptotic protein survivin","volume":"275","author":"Span","year":"2002","journal-title":"Exp. Cell Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1172\/JCI200422222","article-title":"Mitochondrial survivin inhibits apoptosis and promotes tumorigenesis","volume":"114","author":"Dohi","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/S0074-7696(05)47002-3","article-title":"Survivin: A protein with dual roles in mitosis and apoptosis","volume":"247","author":"Wheatley","year":"2005","journal-title":"Int. Rev. Cytol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1042\/BJ20100814","article-title":"Survivin and IAP proteins in cell-death mechanisms","volume":"430","author":"Altieri","year":"2010","journal-title":"Biochem. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/70242","article-title":"Pleiotropic cell-division defects and apoptosis induced by interference with survivin function","volume":"1","author":"Li","year":"1999","journal-title":"Nat. Cell Biol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Conde, M., Michen, S., Wiedemuth, R., Klink, B., Schr\u00f6ck, E., Schackert, G., and Temme, A. (2017). Chromosomal instability induced by increased BIRC5\/Survivin levels affects tumorigenicity of glioma cells. BMC Cancer, 17.","DOI":"10.1186\/s12885-017-3932-y"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1186\/s12943-015-0467-1","article-title":"The twisted survivin connection to angiogenesis","volume":"14","author":"Sanhueza","year":"2015","journal-title":"Mol. Cancer"},{"key":"ref_29","first-page":"270","article-title":"Effects of survivin on angiogenesis in vivo and in vitro","volume":"8","author":"Li","year":"2016","journal-title":"Am. J. Transl. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1186\/1476-4598-13-209","article-title":"Survivin expression promotes VEGF-induced tumor angiogenesis via PI3K\/Akt enhanced \u03b2-catenin\/Tcf-Lef dependent transcription","volume":"13","author":"Valenzuela","year":"2014","journal-title":"Mol. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1093\/nar\/29.10.2041","article-title":"Antisense oligonucleotides selected by hybridisation to scanning arrays are effective reagents in vivo","volume":"29","author":"Sohail","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4989","DOI":"10.1093\/nar\/gkg710","article-title":"Thermodynamic criteria for high hit rate antisense oligonucleotide design","volume":"31","author":"Matveeva","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Leckie, J., and Yokota, T. (2025). Integrating machine learning-based approaches into the design of ASO therapies. Genes, 16.","DOI":"10.20944\/preprints202501.0135.v1"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4145","DOI":"10.1016\/j.csbj.2025.09.022","article-title":"ASOG: AntiSense Oligonucleotide Generator","volume":"27","author":"Kimi","year":"2025","journal-title":"Comput Struct. Biotechnol. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"102186","DOI":"10.1016\/j.omtn.2024.102186","article-title":"ASOptimizer: Optimizing antisense oligonucleotides through deep learning for IDO1 gene regulation","volume":"35","author":"Hwang","year":"2024","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1038\/s41573-021-00162-z","article-title":"Antisense technology: An overview and prospectus","volume":"20","author":"Crooke","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"102953","DOI":"10.1016\/j.omtn.2026.102953","article-title":"Expanding the toolbox: Emerging antisense oligonucleotide mechanisms for modulating gene expression","volume":"37","author":"Trew","year":"2026","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1016\/j.ymthe.2017.06.002","article-title":"RNase H1-dependent antisense oligonucleotides are robustly active in directing RNA cleavage in both the cytoplasm and the nucleus","volume":"25","author":"Liang","year":"2017","journal-title":"Mol. Ther."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrneurol.2017.148","article-title":"Antisense oligonucleotides: The next frontier for treatment of neurological disorders","volume":"14","author":"Rinaldi","year":"2018","journal-title":"Nat. Rev. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6078","DOI":"10.1038\/s41598-019-42523-0","article-title":"Systematic evaluation of 2\u2032-Fluoro modified chimeric antisense oligonucleotide-mediated exon skipping in vitro","volume":"9","author":"Chen","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"5871","DOI":"10.1093\/nar\/gku184","article-title":"Nonsense-mediated decay as a terminating mechanism for antisense oligonucleotides","volume":"42","author":"Ward","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1101\/gad.1941310","article-title":"Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model","volume":"24","author":"Hua","year":"2010","journal-title":"Genes Dev."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11994","DOI":"10.1074\/jbc.272.18.11994","article-title":"2\u2032-O-(2-Methoxy)ethyl-modified anti-intercellular adhesion molecule 1 (ICAM-1) oligonucleotides selectively increase the ICAM-1 mRNA level and inhibit formation of the ICAM-1 translation initiation complex in human umbilical vein endothelial cells","volume":"272","author":"Baker","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"6900","DOI":"10.1093\/nar\/gkz500","article-title":"mRNA levels can be reduced by antisense oligonucleotides via no-go decay pathway","volume":"47","author":"Liang","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e22187","DOI":"10.1002\/ddr.22187","article-title":"Unveiling the potential of antisense oligonucleotides: Mechanisms, therapies, and safety insights","volume":"85","year":"2024","journal-title":"Drug Dev. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"48650","DOI":"10.1021\/acsomega.3c07618","article-title":"Evaluation of chemically modified nucleic acid analogues for splice switching application","volume":"8","author":"Le","year":"2023","journal-title":"ACS Omega"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1080\/17425255.2021.1992382","article-title":"Antisense oligonucleotides: Absorption, distribution, metabolism, and excretion","volume":"17","author":"Shadid","year":"2021","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Le, B.T., Chen, S., and Veedu, R.N. (2024). Rational design of chimeric antisense oligonucleotides on a mixed PO-PS backbone for splice-switching applications. Biomolecules, 14.","DOI":"10.3390\/biom14070883"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"17001","DOI":"10.1039\/D5CC04787K","article-title":"Systematic evaluation of 2\u2032-O-methyl RNA antisense oligonucleotides with limited phosphorothioate linkages for efficient splice switching","volume":"61","author":"Chen","year":"2025","journal-title":"Chem. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4429","DOI":"10.1093\/nar\/25.22.4429","article-title":"The ups and downs of nucleic acid duplex stability: Structure\u2013stability studies on chemically modified DNA\/RNA duplexes","volume":"25","author":"Freier","year":"1997","journal-title":"Nucleic Acids Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1146\/annurev.pharmtox.010909.105654","article-title":"RNA targeting therapeutics: Molecular mechanisms of antisense oligonucleotides as a therapeutic platform","volume":"50","author":"Bennett","year":"2010","journal-title":"Annu Rev. Pharmacol. Toxicol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Singh, S.K., Koshkin, A.A., Wengel, G., and Nielsen, P. (1998). LNA (Locked Nucleic Acids): Synthesis and High-Affinity Nucleic Acid Recognition. Chem. Commun., 455\u2013456.","DOI":"10.1039\/a708608c"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.omtn.2017.09.002","article-title":"Rational design of short locked nucleic acid-modified 2\u2032-O-methyl antisense oligonucleotides for efficient exon-skipping in vitro","volume":"9","author":"Le","year":"2017","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1089\/oli.1.1997.7.187","article-title":"Morpholino antisense oligomers: Design, preparation, and properties","volume":"7","author":"Summerton","year":"1997","journal-title":"Antisense Nucleic Acids Drug Dev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"102548","DOI":"10.1016\/j.omtn.2025.102548","article-title":"Antisense oligonucleotide targeting nicotinamide N-methyltransferase exhibits antitumor effects","volume":"36","author":"Hara","year":"2025","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"102761","DOI":"10.1016\/j.omtn.2025.102761","article-title":"An LNA gapmer antisense oligonucleotide inhibitor of human NNMT","volume":"36","author":"Chen","year":"2025","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"102404","DOI":"10.1016\/j.omtn.2024.102404","article-title":"Discovery and characterization of stereodefined PMO-gapmers targeting tau","volume":"36","author":"Kanatsu","year":"2024","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"102519","DOI":"10.1016\/j.omtn.2025.102519","article-title":"A single stereogenic center matters: Development of stereodefined anti-tau PMO-gapmers","volume":"36","author":"Chen","year":"2025","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.jconrel.2022.10.050","article-title":"Nano drug delivery systems for antisense oligonucleotides (ASO) therapeutics","volume":"352","author":"Ramasamy","year":"2022","journal-title":"J. Control. Release"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s12032-025-02939-3","article-title":"Lipid nanoparticles: A promising tool for nucleic acid delivery in cancer immunotherapy","volume":"42","author":"Abaza","year":"2025","journal-title":"Med. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"113865","DOI":"10.1016\/j.jconrel.2025.113865","article-title":"VPS9D1-AS1 antisense therapy via lipid nanoparticles reprograms cold tumors and enhances immunotherapy in colorectal cancer","volume":"384","author":"Yang","year":"2025","journal-title":"J. Control. Release"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2294","DOI":"10.1093\/nar\/gkx060","article-title":"Characterizing the effect of GalNAc and phosphorothioate backbone on binding of antisense oligonucleotides to the asialoglycoprotein receptor","volume":"45","author":"Schmidt","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"118223","DOI":"10.1016\/j.bmc.2025.118223","article-title":"Screening and evaluation of hydrophobic cell-penetrating peptides for antisense oligonucleotide delivery","volume":"126","author":"Tamura","year":"2025","journal-title":"Bioorg Med. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"McClorey, G., and Banerjee, S. (2018). Cell-penetrating peptides to enhance delivery of oligonucleotide-based therapeutics. Biomedicines, 6.","DOI":"10.3390\/biomedicines6020051"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"838","DOI":"10.3390\/jcm10040838","article-title":"Antibody-oligonucleotide conjugates: A twist to antibody-drug conjugates","volume":"10","author":"Thirumalairajan","year":"2021","journal-title":"J. Clin. Med."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"43727","DOI":"10.1039\/D5RA05904F","article-title":"Enhancing the intracellular delivery of antisense oligonucleotides (ASO): A comparative study of aptamer, vitamin E, and cholesterol ASO conjugates","volume":"15","author":"Balachandran","year":"2025","journal-title":"RSC Adv."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"6029","DOI":"10.1093\/nar\/gkz354","article-title":"Fatty acid conjugation enhances potency of antisense oligonucleotides in muscle","volume":"47","author":"Prakash","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"18035","DOI":"10.1021\/acsomega.0c01463","article-title":"Novel disulfide-bridged bioresponsive antisense oligonucleotide induces efficient splice modulation in muscle myotubes in vitro","volume":"5","author":"Le","year":"2020","journal-title":"ACS Omega"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"102577","DOI":"10.1016\/j.omtn.2025.102577","article-title":"A genome-wide CRISPR screen unveils the endosomal maturation protein WDR91 as a promoter of productive ASO activity in melanoma","volume":"36","author":"Menchon","year":"2025","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"102915","DOI":"10.1016\/j.omtn.2026.102915","article-title":"WDR91, an endosomal maturation protein, promotes antisense oligonucleotide activity","volume":"37","author":"Chen","year":"2026","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"488","DOI":"10.4161\/cc.2.5.500","article-title":"Targeting survivin expression induces cell proliferation defect and subsequent cell death involving mitochondrial pathway in myeloid leukemic cells","volume":"2","author":"Carter","year":"2003","journal-title":"Cell Cycle"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1251\/bpo95","article-title":"The use of antisense oligonucleotides in evaluating survivin as a therapeutic target for radiation sensitization in lung cancer","volume":"6","author":"Shinohara","year":"2004","journal-title":"Biol. Proced. Online"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2840","DOI":"10.1158\/0008-5472.CAN-03-3547","article-title":"Survivin as a therapeutic target for radiation sensitization in lung cancer","volume":"64","author":"Lu","year":"2004","journal-title":"Cancer Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/sj.leu.2403281","article-title":"Inhibition of survivin expression suppresses the growth of aggressive non-Hodgkin\u2019s lymphoma","volume":"18","author":"Ansell","year":"2004","journal-title":"Leukemia"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.1158\/1535-7163.MCT-08-0161","article-title":"SPC3042: A proapoptotic survivin inhibitor","volume":"7","author":"Hansen","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1158\/1535-7163.MCT-10-0756","article-title":"Antisense inhibition of survivin expression as a cancer therapeutic","volume":"10","author":"Carrasco","year":"2011","journal-title":"Mol. Cancer Ther."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e30","DOI":"10.1038\/mtna.2012.19","article-title":"Quantitative analysis of survivin protein expression and its therapeutic depletion by an antisense oligonucleotide in human lung tumors","volume":"1","author":"Olsen","year":"2012","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"4466","DOI":"10.1021\/acs.jmedchem.4c02428","article-title":"NQO1-activatable circular antisense oligonucleotides for tumor-cell-specific survivin gene silencing and antitumor therapy","volume":"68","author":"Zhao","year":"2025","journal-title":"J. Med. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/sj.neo.7900091","article-title":"Down-regulation of survivin by antisense oligonucleotides increases apoptosis, inhibits cytokinesis and anchorage-independent growth","volume":"2","author":"Chen","year":"2000","journal-title":"Neoplasia"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1080\/15257771003597733","article-title":"Down-modulation of survivin expression and inhibition of tumor growth in vivo by EZN-3042, a locked nucleic acid antisense oligonucleotide","volume":"29","author":"Sapra","year":"2010","journal-title":"Nucleosides Nucleot. Nucl."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1530\/ERC-11-0207","article-title":"Knockdown of survivin (BIRC5) causes apoptosis in neuroblastoma via mitotic catastrophe","volume":"18","author":"Lamers","year":"2011","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1182\/blood-2011-04-351239","article-title":"Targeting survivin overcomes drug resistance in acute lymphoblastic leukemia","volume":"118","author":"Park","year":"2011","journal-title":"Blood"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/leu.2011.199","article-title":"Endogenous knockdown of survivin improves chemotherapeutic response in ALL models","volume":"26","author":"Morrison","year":"2012","journal-title":"Leukemia"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Thamm, D.H., Joseph, J.K., Rose, B.J., Meuten, T.K., and Weishaar, K.M. (2020). Phase-I trial of survivin inhibition with EZN-3042 in dogs with spontaneous lymphoma. BMC Vet. Res., 16.","DOI":"10.1186\/s12917-020-02317-3"},{"key":"ref_85","first-page":"2805","article-title":"A novel antisense oligonucleotide targeting survivin expression induces apoptosis and sensitizes lung cancer cells to chemotherapy","volume":"60","author":"Olie","year":"2000","journal-title":"Cancer Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"193","DOI":"10.3748\/wjg.v11.i2.193","article-title":"Survivin antisense compound inhibits proliferation and promotes apoptosis in liver cancer cells","volume":"11","author":"Dai","year":"2005","journal-title":"World J. Gastroenterol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"501","DOI":"10.4149\/neo_2010_06_501","article-title":"Antisense oligonucleotide targeting survivin inhibits growth by inducing apoptosis in human osteosarcoma cells MG-63","volume":"57","author":"Wu","year":"2010","journal-title":"Neoplasma"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1089\/1545457041526290","article-title":"Use of siRNAs and antisense oligonucleotides against survivin RNA to inhibit steps leading to tumor angiogenesis","volume":"14","author":"Coma","year":"2004","journal-title":"Oligonucleotides"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1089\/oli.2006.16.365","article-title":"Suppression of tumor growth using antisense oligonucleotide against survivin in an orthotopic transplant model of human hepatocellular carcinoma in nude mice","volume":"16","author":"Sun","year":"2006","journal-title":"Oligonucleotides"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"13336","DOI":"10.1039\/D4RA01925C","article-title":"Inhibition of survivin by 2\u2032-O-methyl phosphorothioate-modified steric-blocking antisense oligonucleotides","volume":"14","author":"Li","year":"2024","journal-title":"RSC Adv."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/j.1365-2125.2010.03836.x","article-title":"Integrated analysis of preclinical data to support the design of the first in man study of LY2181308, a second generation antisense oligonucleotide","volume":"71","author":"Callies","year":"2011","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"6150","DOI":"10.1158\/1078-0432.CCR-10-1932","article-title":"Tumor survivin is downregulated by the antisense oligonucleotide LY2181308: A proof-of-concept, first-in-human dose study","volume":"16","author":"Talbot","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1007\/s00280-010-1506-7","article-title":"Phase I study of LY2181308, an antisense oligonucleotide against survivin, in patients with advanced solid tumors","volume":"68","author":"Tanioka","year":"2011","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1007\/s10637-013-9935-x","article-title":"Safety and pharmacokinetics of the antisense oligonucleotide (ASO) LY2181308 as a single-agent or in combination with idarubicin and cytarabine in patients with refractory or relapsed acute myeloid leukemia (AML)","volume":"31","author":"Erba","year":"2013","journal-title":"Investig. New Drugs"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.eururo.2013.10.039","article-title":"A randomised phase 2 study combining LY2181308 sodium (survivin antisense oligonucleotide) with first-line docetaxel\/prednisone in patients with castration-resistant prostate cancer","volume":"65","author":"Wiechno","year":"2014","journal-title":"Eur. Urol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1097\/JTO.0000000000000285","article-title":"Evaluation of antitumor activity using change in tumor size of the survivin antisense oligonucleotide LY2181308 in combination with docetaxel for second-line treatment of patients with non-small-cell lung cancer: A randomized open-label phase II study","volume":"9","author":"Natale","year":"2014","journal-title":"J. Thorac. Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1053\/j.ajkd.2010.09.024","article-title":"Association of long-term administration of the survivin mRNA-targeted antisense oligonucleotide LY2181308 with reversible kidney injury in a patient with metastatic melanoma","volume":"57","author":"Herrington","year":"2011","journal-title":"Am. J. Kidney Dis."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1097\/MPH.0b013e3182a8f58f","article-title":"A phase I study of EZN-3042, a novel survivin messenger ribonucleic acid (mRNA) antagonist, administered in combination with chemotherapy in children with relapsed acute lymphoblastic leukemia (ALL): A report from the therapeutic advances in childhood leukemia and lymphoma (TACL) consortium","volume":"36","author":"Raetz","year":"2014","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/nbt.3779","article-title":"Cellular uptake and trafficking of antisense oligonucleotides","volume":"35","author":"Crooke","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"6518","DOI":"10.1093\/nar\/gkw236","article-title":"The delivery of therapeutic oligonucleotides","volume":"44","author":"Juliano","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/nbt.3802","article-title":"Overcoming cellular barriers for RNA therapeutics","volume":"35","author":"Dowdy","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1093\/nar\/gkz1132","article-title":"Hybridization-mediated off-target effects of splice-switching antisense oligonucleotides","volume":"48","author":"Scharner","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1111\/gtc.12730","article-title":"Evaluation of off-target effects of gapmer antisense oligonucleotides using human cells","volume":"24","author":"Yoshida","year":"2019","journal-title":"Genes Cells"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1093\/nar\/gkx1239","article-title":"Chemistry, mechanism and clinical status of antisense oligonucleotides and duplex RNAs","volume":"46","author":"Shen","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"100254","DOI":"10.1016\/j.slasd.2025.100254","article-title":"Off-target effects of oligonucleotides and approaches of preclinical assessments","volume":"35","author":"Ruan","year":"2025","journal-title":"SLAS Discov."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s43856-023-00419-1","article-title":"N\u2009=\u20091 Collaborative. Possibilities and limitations of antisense oligonucleotide therapies for the treatment of monogenic disorders","volume":"4","author":"Lauffer","year":"2024","journal-title":"Commun. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"114196","DOI":"10.1016\/j.bcp.2020.114196","article-title":"Antisense drug discovery and development technology considered in a pharmacological context","volume":"189","author":"Crooke","year":"2021","journal-title":"Biochem Pharmacol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/13\/2283\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T08:32:47Z","timestamp":1782808367000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/13\/2283"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":107,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["molecules31132283"],"URL":"https:\/\/doi.org\/10.3390\/molecules31132283","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]}}}