Assessing single-stranded oligonucleotide drug-induced effects in vitro reveals key risk factors for thrombocytopenia
Open accessAbstract
Single-stranded oligonucleotides (ON) comprise a promising therapeutic platform that enables selective modulation of currently undruggable targets. The development of novel ON drug candidates has demonstrated excellent efficacy, but in certain cases also some safety liabilities were reported. Among them are events of thrombocytopenia, which have recently been evident in late stage trials with ON drugs. The underlying mechanisms are poorly understood and the risk for ON candidates causing such events cannot be sufficiently assessed pre-clinically. We investigated potential thrombocytopenia risk factors of ONs and implemented a set of in vitro assays to assess these risks. Our findings support previous observations that phosphorothioate (PS)-ONs can bind to platelet proteins such as platelet collagen receptor glycoprotein VI (GPVI) and activate human platelets in vitro to various extents. We also show that these PS-ONs can bind to platelet factor 4 (PF4). Binding to platelet proteins and subsequent activation correlates with ON length and connected to this, the number of PS in the backbone of the molecule. Moreover, we demonstrate that locked nucleic acid (LNA) ribosyl modifications in the wings of the PS-ONs strongly suppress binding to GPVI and PF4, paralleled by markedly reduced platelet activation. In addition, we provide evidence that PS-ONs do not directly affect hematopoietic cell differentiation in culture but at higher concentrations show a pro-inflammatory potential, which might contribute to platelet activation. Overall, our data confirm that certain molecular attributes of ONs are associated with a higher risk for thrombocytopenia. We propose that applying the in vitro assays discussed here during the lead optimization phase may aid in deprioritizing ONs with a potential to induce thrombocytopenia.
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The most advanced CNS-active ASO scaffold utilizes a mixed backbone configuration with at least 70-80% PS content, maintaining efficacy and distribution with minimal risk of toxic phenotypes.
“The most advanced CNS-active ASO scaffold utilizes a mixed backbone configuration with at least 70–80% PS content. This modification maintains efficacy and distribution with minimal risk of toxic phenotypes 13, 14 via mechanisms that are not fully understood15.”
From A divalent siRNA chemical scaffold for potent and sustained modulation of gene expression throughout the central nervous system (2019) · cites this paper as [14]
The Discussion (page not provided) reports that reducing PS content may reduce platelet activation and thrombocytopenia risk, and that LNA modifications improve binding to RNA targets. But the Methods describe the tested oligonucleotides as fully phosphorothioated; the paper does not establish a CNS-active mixed-backbone scaffold with 70–80% PS content or show maintained efficacy and distribution. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThrombocytopenia (low platelet count) has been reported as a PS-mediated rare adverse event.
“In addition, we found no measurable changes in blood chemistry or cell counts (Supplementary Fig. 20), which is particularly important because thrombocytopenia (low platelet count) has been reported as a PS-mediated rare adverse event13, 14.”
From A divalent siRNA chemical scaffold for potent and sustained modulation of gene expression throughout the central nervous system (2019) · cites this paper as [14]
The Introduction (page unavailable) reports rare platelet-count reductions and cases of severe thrombocytopenia in trials of phosphorothioate oligonucleotides. But the Discussion (page unavailable) says the clinical mechanism remains unknown and may be multifactorial, so the paper does not establish that PS itself mediated those events. (LLM, conf=0.86)
Experimental — accuracy not yet measured
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Cites
Bennett, C. F., & Swayze, E. E. (2010) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.010909.105654 · Cited by 1,381 · see citing works
Heparin‐induced thrombocytopenia: pathogenesis and management
Warkentin, T. E. (2003) · British Journal of Haematology · doi:10.1046/j.1365-2141.2003.04334.x · Cited by 548 · see citing works
Graham, M. J., Lee, R. G., Bell, T. A., Fu, W., Mullick, A. E., Alexander, V. J., Singleton, W., Viney, N., Geary, R., Su, J., et al. (2013) · Circulation Research · doi:10.1161/circresaha.111.300367 · Cited by 377 · see citing works
Antisense Oligonucleotide Therapies
Frazier, K. S. (2014) · Toxicologic Pathology · doi:10.1177/0192623314551840 · Cited by 335 · see citing works
Preclinical and Clinical Advances of GalNAc-Decorated Nucleic Acid Therapeutics
Huang, Y. (2016) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2016.12.003 · Cited by 295 · see citing works
(2010) · CRC Press eBooks · doi:10.1201/9781420002546 · Cited by 270 · see citing works
Burel, S. A., Hart, C. E., Cauntay, P., Hsiao, J., Machemer, T., Katz, M., Watt, A., Bui, H., Younis, H. S., Sabripour, M., et al. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv1210 · Cited by 217 · see citing works
Burdick, A. D., Sciabola, S., Mantena, S. R., Hollingshead, B. D., Stanton, R. V., Warneke, J. A., Zeng, M., Martsen, E., Medvedev, A. V., Makarov, S. S., et al. (2014) · Nucleic Acids Research · doi:10.1093/nar/gku142 · Cited by 179 · see citing works
Analysis of the Interaction of Platelet Collagen Receptor Glycoprotein VI (GPVI) with Collagen
Miura, Y., Takahashi, T., Jung, S. M., & Moroi, M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204029200 · Cited by 170 · see citing works
Drug-Induced Immune-Mediated Thrombocytopenia — From Purpura to Thrombosis
Warkentin, T. E. (2007) · New England Journal of Medicine · doi:10.1056/nejmp068309 · Cited by 166 · see citing works
Platelet-leukocyte crosstalk: Linking proinflammatory responses to procoagulant state
Ghasemzadeh, M., & Hosseini, E. (2012) · Thrombosis Research · doi:10.1016/j.thromres.2012.11.028 · Cited by 163 · see citing works
Jaax, M. E., Krauel, K., Marschall, T., Brandt, S. V., Gansler, J., Fürll, B., Appel, B., Fischer, S., Block, S., Helm, C. A., et al. (2013) · Blood · doi:10.1182/blood-2013-01-478966 · Cited by 162 · see citing works
Chemically Modified Oligonucleotides Exhibit Decreased Immune Stimulation in Mice
Henry, S. P., Stecker, K., Brooks, D., Monteith, D., Conklin, B., & Bennett, C. F. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)35315-7 · Cited by 152 · see citing works
Arepally, G. M., Kamei, S., Park, K. S., Kamei, K., Li, Z. Q., Liu, W., Siegel, D. L., Kisiel, W., Cines, D. B., & Poncz, M. (2000) · Blood · doi:10.1182/blood.v95.5.1533.005k01_1533_1540 · Cited by 136 · see citing works
Crooke, S. T., Baker, B. F., Witztum, J. L., Kwoh, T. J., Pham, N. C., Salgado, N., McEvoy, B. W., Cheng, W., Hughes, S. G., Bhanot, S., et al. (2017) · Nucleic Acid Therapeutics · doi:10.1089/nat.2016.0650 · Cited by 129 · see citing works
Heparin-Induced Thrombocytopenia
Arepally, G. M., & Ortel, T. L. (2010) · Annual Review of Medicine · doi:10.1146/annurev.med.042808.171814 · Cited by 129 · see citing works
Henry, S. P., Bolte, H. F., Auletta, C. S., & Kornbrust, D. J. (1997) · Toxicology · doi:10.1016/s0300-483x(97)03661-5 · Cited by 118 · see citing works
Crooke, S. T., Baker, B. F., Kwoh, T. J., Cheng, W., Schulz, D. J., Xia, S., Salgado, N. R., Bui, H., Hart, C. E., Burel, S. A., et al. (2016) · Molecular Therapy · doi:10.1038/mt.2016.136 · Cited by 118 · see citing works
Phosphorothioate Oligonucleotides Inhibit the Intrinsic Tenase Complex
Sheehan, J. P., & Lan, H.-C. (1998) · Blood · doi:10.1182/blood.v92.5.1617 · Cited by 118 · see citing works
Anti-platelet factor 4/polyanion antibodies mediate a new mechanism of autoimmunity
Nguyen, T., Medvedev, N., Delcea, M., & Greinacher, A. (2017) · Nature Communications · doi:10.1038/ncomms14945 · Cited by 117 · see citing works
Phosphorothioate backbone modifications of nucleotide-based drugs are potent platelet activators
Flierl, U., Nero, T. L., Lim, B., Arthur, J. F., Yao, Y., Jung, S. M., Gitz, E., Pollitt, A. Y., Zaldivia, M. T. K., Jandrot-Perrus, M., et al. (2015) · Journal of Experimental Medicine · doi:10.1084/jem.20140391 · Cited by 114 · see citing works
Jung, S. M., Moroi, M., Soejima, K., Nakagaki, T., Miura, Y., Berndt, M. C., Gardiner, E. E., Howes, J., Pugh, N., Bihan, D. G., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.359125 · Cited by 101 · see citing works
Henry, S. P., TAYLOR, J., MIDGLEY, L., Levin, A. A., & Kornbrust, D. J. (1997) · Antisense and Nucleic Acid Drug Development · doi:10.1089/oli.1.1997.7.473 · Cited by 94 · see citing works
Senn, J. J., Burel, S. A., & Henry, S. P. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.084004 · Cited by 88 · see citing works
Cines, D. B., Rauova, L., Arepally, G. M., Reilly, M. P., McKenzie, S. E., Sachais, B. S., & Poncz, M. (2007) · Journal of Clinical Apheresis · doi:10.1002/jca.20109 · Cited by 86 · see citing works
Brandt, S. V., Krauel, K., Gottschalk, K. E., Renné, T., Helm, C. A., Greinacher, A., & Block, S. (2014) · Thrombosis and Haemostasis · doi:10.1160/th13-08-0634 · Cited by 84 · see citing works
Seth, P. P., Jazayeri, A., Yu, J., Allerson, C. R., Bhat, B., & Swayze, E. E. (2012) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2012.34 · Cited by 44 · see citing works
Mangsbo, S. M., Sanchez, J., Anger, K., Lambris, J. D., Ekdahl, K. N., Loskog, A. S., Nilsson, B., & Tötterman, T. H. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0902374 · Cited by 42 · see citing works
Henry, S. P., Seguin, R. M., Cavagnaro, J. A., Berman, C., Tepper, J., & Kornbrust, D. J. (2016) · Nucleic Acid Therapeutics · doi:10.1089/nat.2015.0593 · Cited by 42 · see citing works
Sewing, S., Boess, F., Moisan, A., Bertinetti‐Lapatki, C., Minz, T., Hedtjaern, M., Tessier, Y., Schuler, F., Singer, T., & Roth, A. B. (2016) · PLoS ONE · doi:10.1371/journal.pone.0159431 · Cited by 39 · see citing works
Self-citationControversies in the Cellular Pharmacology of Oligodeoxynucleotides
Stein, C. (1997) · Antisense and Nucleic Acid Drug Development · doi:10.1089/oli.1.1997.7.207 · Cited by 39 · see citing works
Toxicologic Properties of 2-O-Methoxyethyl Chimeric Antisense Inhibitors in Animals and Man
Henry, S. P., Kim, T., Kramer-Stickland, K., Zanardi, T. A., Fey, R. A., & Levin, A. A. (2007) · CRC Press eBooks · doi:10.1201/9780849387951-20 · Cited by 37 · see citing works
A snapshot of biologic drug development
Andrews, L., Ralston, S. L., Blomme, E. A. G., & Barnhart, K. F. (2015) · Human & Experimental Toxicology · doi:10.1177/0960327115603594 · Cited by 36 · see citing works
Weil, C. S. (1964) · The Annals of Occupational Hygiene · doi:10.1093/annhyg/7.4.392 · Cited by 34 · see citing works
Olaharski, A. J., Uppal, H., Cooper, M., Platz, S. J., Zabka, T. S., & Kolaja, K. L. (2009) · Toxicology Letters · doi:10.1016/j.toxlet.2009.03.012 · Cited by 34 · see citing works
Moisan, A., Gubler, M., Zhang, J. D., Tessier, Y., Erichsen, K. D., Sewing, S., Gérard, R., Avignon, B., Huber, S., Benmansour, F., et al. (2016) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2016.11.006 · Cited by 33 · see citing works
Self-citationThe unique immunological features of heparin‐induced thrombocytopenia
Staibano, P., Arnold, D. M., Bowdish, D. M. E., & Nazy, I. (2017) · British Journal of Haematology · doi:10.1111/bjh.14603 · Cited by 30 · see citing works
Kakiuchi-Kiyota, S., Whiteley, L. O., Ryan, A. M., & Mathialagan, N. (2015) · Nucleic Acid Therapeutics · doi:10.1089/nat.2015.0576 · Cited by 30 · see citing works
Koch, T. (2013) · Current Physical Chemistry · doi:10.2174/1877946811303010009 · Cited by 20 · see citing works
Antier, N., Quenot, J., Doise, J., Noël, R., Demaistre, E., & Devilliers, H. (2014) · Annals of Intensive Care · doi:10.1186/s13613-014-0024-x · Cited by 18 · see citing works
High-throughputin vitrohemotoxicity testing andin vitrocross-platform comparative toxicity
Rich, I. N. (2007) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.3.2.295 · Cited by 18 · see citing works
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Cited by
Sorted by citations
Täubel, J., Hauke, W., Rump, S., Viereck, J., Bátkai, S., Poetzsch, J., Rode, L., Weigt, H., Genschel, C., Lorch, U., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehaa898 · Cited by 397 · see citing works
Delivery of oligonucleotide‐based therapeutics: challenges and opportunities
Hammond, S. M., Aartsma-Rus, A. M., Alves, S., Borgos, S. E., Buijsen, R. A. M., Collin, R. W. J., Covello, G., Denti, M. A., Desviat, L. R., Echevarría, L., et al. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202013243 · Cited by 395 · see citing works
Nissen, S. E., Wolski, K., Balog, C., Swerdlow, D. I., Scrimgeour, A., Rambaran, C., Wilson, R. J., Boyce, M., Ray, K. K., Cho, L., et al. (2022) · JAMA · doi:10.1001/jama.2022.5050 · Cited by 308 · see citing works
Alterman, J. F., Godinho, B. M. D. C., Hassler, M. R., Ferguson, C. M., Echeverria, D., Sapp, E., Haraszti, R. A., Coles, A. H., Conroy, F., Miller, R., et al. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0205-0 · Cited by 227 · see citing works
RNA Therapeutics in Cardiovascular Disease
Lucas, T., Bonauer, A., & Dimmeler, S. (2018) · Circulation Research · doi:10.1161/circresaha.117.311311 · Cited by 158 · see citing works
Targeting RNA : A Transformative Therapeutic Strategy
Yin, W., & Rogge, M. C. (2019) · Clinical and Translational Science · doi:10.1111/cts.12624 · Cited by 147 · see citing works
Considerations in the Preclinical Assessment of the Safety of Antisense Oligonucleotides
Goyenvalle, A., Jimenez-Mallebrera, C., van Roon‐Mom, W., Sewing, S., Krieg, A. Μ., Arechavala‐Gomeza, V., & Andersson, P. U. (2022) · Nucleic Acid Therapeutics · doi:10.1089/nat.2022.0061 · Cited by 98 · see citing works
Self-citationLandmesser, U., Haghikia, A., Leiter, L. A., Wright, R. S., Kallend, D., Wijngaard, P., Stoekenbroek, R., Kastelein, J. J., & Ray, K. K. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvaa077 · Cited by 83 · see citing works
The Nonclinical Safety Profile of GalNAc-conjugated RNAi Therapeutics in Subacute Studies
Janas, M. M., Harbison, C. E., Perry, V. K., Carito, B. A., Sutherland, J. E., Vaishnaw, A. K., Keirstead, N. D., & Warner, G. L. (2018) · Toxicologic Pathology · doi:10.1177/0192623318792537 · Cited by 82 · see citing works
A holistic analysis of the intrinsic and delivery-mediated toxicity of siRNA therapeutics
Ranjbar, S., Zhong, X., Manautou, J. E., & Lü, X. (2023) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2023.115052 · Cited by 69 · see citing works
Yuen, M., Heo, J., Kumada, H., Suzuki, F., Suzuki, Y., Xie, Q., Jia, J., Karino, Y., Hou, J., Chayama, K., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.05.031 · Cited by 55 · see citing works
Pharmacokinetics and Proceedings in Clinical Application of Nucleic Acid Therapeutics
Herkt, M., & Thum, T. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.11.008 · Cited by 55 · see citing works
The Neonatal and Juvenile Pig in Pediatric Drug Discovery and Development
Ayuso, M., Buyssens, L. A., Stroe, M., Valenzuela, A., Allegaert, K., Smits, A., Annaert, P., Mulder, A., Carpentier, S., Ginneken, C. J. V., et al. (2020) · Pharmaceutics · doi:10.3390/pharmaceutics13010044 · Cited by 43 · see citing works
Narayanan, P., Shen, L., Curtis, B. R., Bourdon, M. A., Nolan, J. P., Gupta, S., Hoffmaster, C. M., Zhou, F., Christian, B., Schaubhut, J., et al. (2018) · Toxicological Sciences · doi:10.1093/toxsci/kfy119 · Cited by 39 · see citing works
Andersson, P. U., Burel, S. A., Estrella, H., Foy, J. W.-D., Hagedorn, P., Harper, T. A., Henry, S. P., Hoflack, J.-C., Holgersen, E. M., Levin, A. A., et al. (2025) · Nucleic Acid Therapeutics · doi:10.1089/nat.2024.0072 · Cited by 31 · see citing works
Aupy, P., Echevarría, L., Relizani, K., Zarrouki, F., Haeberli, A., Komisarski, M., Tensorer, T., Jouvion, G., Svinartchouk, F., Garcı́a, L., et al. (2019) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2019.11.020 · Cited by 29 · see citing works
Antisense therapies in neurological diseases
de Courssou, J.-B. B., Dürr, A., Adams, D., Corvol, J., & Mariani, L. (2021) · Brain · doi:10.1093/brain/awab423 · Cited by 28 · see citing works
Preparing for Patient-Customized N-of-1 Antisense Oligonucleotide Therapy to Treat Rare Diseases
Wilton-Clark, H., Yan, E., & Yokota, T. (2024) · Genes · doi:10.3390/genes15070821 · Cited by 27 · see citing works
Making Sense of Antisense Oligonucleotide Therapeutics Targeting Bcl-2
Gagliardi, M. E., & Ashizawa, A. T. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14010097 · Cited by 26 · see citing works
Preclinical Safety Assessment of Therapeutic Oligonucleotides
Andersson, P. U. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2010-6_25 · Cited by 25 · see citing works
Huang, S., Zhou, Y., Zhang, Y., Liu, N., Liu, J., Liu, L., & Fan, C. (2023) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-023-07492-7 · Cited by 25 · see citing works
Gogate, A., Belcourt, J., Shah, M., Wang, A., Frankel, A., Kolmel, H., Chalon, M., Stephen, P., Kolli, A., Tawfik, S. M., et al. (2023) · Pharmacological Reviews · doi:10.1124/pharmrev.123.000815 · Cited by 25 · see citing works
Targeted Degradation of Structured RNAs via Ribonuclease-Targeting Chimeras (RiboTacs)
Haj-Yahia, S., Nandi, A., & Benhamou, R. I. (2023) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2023.2224960 · Cited by 22 · see citing works
Nucleic acid-based therapeutics for the treatment of central nervous system disorders
McCartan, R., Khorkova, O., Volmar, C., & Wahlestedt, C. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2023.1250276 · Cited by 22 · see citing works
The Interface of Therapeutics and Genomics in Cardiovascular Medicine
Magavern, E. F., Kaski, J. C., Turner, R. M., Janmohamed, A., Borry, P., & Pirmohamed, M. (2021) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-021-07149-3 · Cited by 21 · see citing works
Editing Approaches to Treat Alpha-1 Antitrypsin Deficiency
Erion, D. M., Liu, L. Y., Brown, C. R., Rennard, S. I., & Farah, H. (2024) · CHEST Journal · doi:10.1016/j.chest.2024.09.038 · Cited by 21 · see citing works
Antisense oligonucleotides and nucleic acids generate hypersensitive platelets
Zaslavsky, A., Adams, M. P., Cao, X., Yamaguchi, A. A., Henderson, J., Busch-Østergren, P., Udager, A. M., Pitchiaya, S., Tourdot, B. E., Kasputis, T., et al. (2021) · Thrombosis Research · doi:10.1016/j.thromres.2021.01.006 · Cited by 16 · see citing works
Grudzinska‐Goebel, J., Braun, M., Chen, L., Gupta, S., Lohmann, S., Morais, P., Niu, T., Tarcsa, E., Tourdot, S., Youssef, A. S., et al. (2025) · Nucleic Acid Therapeutics · doi:10.1177/21593337251387423 · Cited by 16 · see citing works
Slingsby, M. H. L., Vijey, P., Tsai, I., Roweth, H. G., Couldwell, G. C., Wilkie, A. R., Gaus, H. J., Goolsby, J. M., Okazaki, R. A., Terkovich, B. E., et al. (2021) · Haematologica · doi:10.3324/haematol.2020.260059 · Cited by 14 · see citing works
Rider, D. A., Chivers, S., Aretz, J., Eisermann, M., Löffler, K., Hauptmann, J., Morrison, E., & Campion, G. (2022) · Toxicological Sciences · doi:10.1093/toxsci/kfac067 · Cited by 14 · see citing works
Andersson, P. U., & den Besten, C. (2019) · Royal Society of Chemistry eBooks · doi:10.1039/9781788015714-00474 · Cited by 14 · see citing works
Shaharyar, M. A., Bhowmik, R., Al-Abbasi, F. A., AlGhamdi, S. A., Alghamdi, A. M., Sarkar, A., Kazmi, I. A., & Karmakar, S. (2023) · Vaccines · doi:10.3390/vaccines11020241 · Cited by 12 · see citing works
Valenzuela, A., Ayuso, M., Buyssens, L. A., Bars, C., Ginneken, C. J. V., Tessier, Y., & Cruchten, S. J. M. V. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15041112 · Cited by 11 · see citing works
Self-citationHarada, K., Wenlong, W., & Shinozawa, T. (2024) · Scientific Reports · doi:10.1038/s41598-024-64063-y · Cited by 9 · see citing works
The mechanism of thrombocytopenia caused by cholesterol-conjugated antisense oligonucleotides
Harada, K., Furukawa, H., Kohara, H., Nishimura, K., Komori, H., Okai, Y., Arai, Y., Yamamoto, Y., Yamamoto, K., Imanishi, A., et al. (2023) · Toxicology in Vitro · doi:10.1016/j.tiv.2023.105569 · Cited by 9 · see citing works
Ow, J. R., Imagawa, E., Chen, F., Cher, W. Y., Chan, S. Y. T., Gurrampati, R. R., Ramadass, V., Loke, M. F., Tabaglio, T., Nishida, H., et al. (2025) · Journal of Hepatology · doi:10.1016/j.jhep.2025.02.007 · Cited by 7 · see citing works
Ohara, M., Nagata, T., Kuwahara, H., Yoshida‐Tanaka, K., Toide, N., Takagi, K., Sato, K., Takenaka, T., Nakakariya, M., Miyata, K., et al. (2024) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2024.102289 · Cited by 6 · see citing works
Characterization of the TLR9-Activating Potential of LNA-Modified Antisense Oligonucleotides
Riera-Tur, I., Hinterdobler, J., Maaske, A., Sadewasser, A., Schell, M., Sekar, J., Michel, S., Klar, R., & Jaschinski, F. (2024) · Nucleic Acid Therapeutics · doi:10.1089/nat.2024.0013 · Cited by 6 · see citing works
Johansson, K. E., Maouia, A., Rebetz, J., Marcoux, G., Shannon, O., Italiano, J. E., Narayanan, P., Henry, S. P., Shen, L., & Semple, J. W. (2024) · Journal of Thrombosis and Haemostasis · doi:10.1016/j.jtha.2024.08.003 · Cited by 5 · see citing works
Opening new frontiers with catalytic nucleic acids in miRNA inhibition
Patutina, O., Miroshnichenko, S. K., Chiglintseva, D., & Аркадьевна, З. М. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1604711 · Cited by 3 · see citing works
New approach methodologies to assess wanted and unwanted drugs-induced immunostimulation
Bettinsoli, V., Melzi, G., Marchese, I., Pantaleoni, S., Passoni, F. C., & Corsini, E. (2025) · Current Research in Toxicology · doi:10.1016/j.crtox.2025.100222 · Cited by 2 · see citing works
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Dezfouli, S. A., Uludağ, H., Nasrullah, M., Rajendran, A. P., & Remant, K. C. B. (2026) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2026.115780 · Cited by 2 · see citing works
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Matsuda-Kawabata, S., Nagata, T., Yanagidaira, M., Ihara, K., Ohyagi, M., Kaburagi, H., Yoshida‐Tanaka, K., Sasaki, A., Abe, A., Ebihara, S., et al. (2026) · Nucleic Acids Research · doi:10.1093/nar/gkag007 · Cited by 2 · see citing works
Decoding RNA regulation: Challenges and opportunities for RNA‐based therapies in Europe
Lewis, O. C., Leopold, C., Hoek, J. M., Schiffelers, R. M., & Bruin, M. L. D. (2026) · British Journal of Clinical Pharmacology · doi:10.1002/bcp.70577 · Cited by 1 · see citing works
Meta-analysis of adverse events in clinical studies with antisense oligonucleotide therapies
Vermeer, C., Venema, R. R., Birnie, E., Bolling, M. C., Knoers, N. V. A. M., Bremer, J., & van den Akker, P. C. (2026) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2026.102976 · Cited by 1 · see citing works
Inclisiran: new era of lipid-lowering therapy?
Beneš, J. (2023) · Cor et Vasa · doi:10.33678/cor.2022.043 · Cited by 1 · see citing works
Les thérapies antisens en neurologie
de Courssou, J.-B. B., & Mariani, L. (2023) · Pratique Neurologique - FMC · doi:10.1016/j.praneu.2023.08.001 · Cited by 1 · see citing works
Faculty Opinions recommendation of Targeting RNA: A transformative therapeutic strategy.
Fletcher, S. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.734999550.793560195
(2024) · Frontiers research topics · doi:10.3389/978-2-8325-4801-1
Park, S., Kim, S., Kim, S., Shin, K.-S., Kang, C., Hong, E., Im, W., Jeong, J., Yu, W., Ko, K., et al. (2025) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2025.117503
García-Morin, A., Orozco-Sepúlveda, R., Juarez-Vargas, Y., Banuelos, C., Gutiérrez-Zubiate, I., & Rosas-Acosta, G. (2026) · Research Square · doi:10.21203/rs.3.rs-9361591/v1
- Authors
- Sewing, S., Roth, A. B., Winter, M., Dieckmann, A., Bertinetti-Lapatki, C., Tessier, Y., McGinnis, C., Huber, S., Koller, E., Ploix, C., Reed, J. C., Singer, T., & Rothfuss, A.
- Affiliations
- F. Hoffmann-La Roche AG (CH)
- Roche (Denmark) (DK)
- Corresponding author
- Sewing, Sabine
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2017-11-06
- Volume
- 12
- Issue
- 11
- Pages
- e0187574
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC5673186
- OpenAlex
- W2767260707
- Cited by
- 52
- References
- 41
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 7 · 2023: 10 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 3
- FWCI
- 2.74
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- F. Hoffmann-La Roche
- Topics
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Health Sciences › Medicine › Surgery › Heparin-Induced Thrombocytopenia and Thrombosis
- Keywords
- single-stranded oligonucleotides, thrombocytopenia, phosphorothioate oligonucleotides, platelet activation, glycoprotein VI, platelet factor 4, locked nucleic acid, pro-inflammatory effects, hematopoietic differentiation, oligonucleotide length, lead optimization
- MeSH terms
- Bone Marrow, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Oligonucleotides, Platelet Membrane Glycoproteins, Protein Binding, Risk Factors, Thrombocytopenia, Platelet Activation, Surface Plasmon Resonance
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