{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T16:59:53Z","timestamp":1792515593522,"version":"4.5.0"},"reference-count":103,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T00:00:00Z","timestamp":1733788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003569","name":"Ministry of Food and Drug Safety","doi-asserted-by":"publisher","award":["22213MFDS421"],"award-info":[{"award-number":["22213MFDS421"]}],"id":[{"id":"10.13039\/501100003569","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004332","name":"Seoul National University Hospital","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004332","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arch Toxicol"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The increasing use of SARS-CoV-2 mRNA vaccines has raised concerns about their potential toxicological effects, necessitating further investigation to ensure their safety. To address this issue, we aimed to evaluate the toxicological effects of SARS-CoV-2 mRNA vaccine candidates formulated with four different types of lipid nanoparticles in ICR mice, focusing on repeated doses and administration routes. We conducted an extensive analysis in which mice received the mRNA vaccine candidates intramuscularly (50 \u03bcg\/head) twice at 2-week intervals, followed by necropsy at 2 and 14 dpsi (days post-secondary injection). In addition, we performed a repeated dose toxicity test involving three, four, or five doses and compared the toxicological outcomes between intravenous and intramuscular routes. Our findings revealed that all vaccine candidates significantly induced SARS-CoV-2 spike protein-specific IgG and T cell responses. However, at 2 dpsi, there was a notable temporary decrease in lymphocyte and reticulocyte counts, anemia-related parameters, and significant increases in cardiac damage markers, troponin-I and NT-proBNP. Histopathological analysis revealed severe inflammation and necrosis at the injection site, decreased erythroid cells in bone marrow, cortical atrophy of the thymus, and increased spleen cellularity. While most toxicological changes observed at 2 dpsi had resolved by 14 dpsi, spleen enlargement and injection site damage persisted. Furthermore, repeated doses led to the accumulation of toxicity, and different administration routes resulted in distinct toxicological phenotypes. These findings highlight the potential toxicological risks associated with mRNA vaccines, emphasizing the necessity to carefully consider administration routes and dosage regimens in vaccine safety evaluations, particularly given the presence of bone marrow and immune organ toxicity, which, though eventually reversible, remains a serious concern.<\/jats:p>","DOI":"10.1007\/s00204-024-03912-1","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T23:40:12Z","timestamp":1733787612000},"page":"755-773","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Impact of administration routes and dose frequency on the toxicology of SARS-CoV-2 mRNA vaccines in mice model"],"prefix":"10.1007","volume":"99","author":[{"given":"Jae-Hun","family":"Ahn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jisun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gahyun","family":"Roh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na-Young","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Jin","family":"Bae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Euna","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kang-Min","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Eun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo-Jung","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soyeon","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung Pil","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun-Kyoung","family":"Bang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyochang","family":"Keum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Hwan","family":"Nam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9485-516X","authenticated-orcid":false,"given":"Byeong-Cheol","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,10]]},"reference":[{"issue":"1","key":"3912_CR1","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1161\/01.CIR.88.1.101","volume":"88","author":"JE Adams 3rd","year":"1993","unstructured":"Adams JE 3rd, Bodor GS, Davila-Roman VG, Delmez JA, Apple FS, Ladenson JH, Jaffe AS (1993) Cardiac troponin I: a marker with high specificity for cardiac injury. Circulation 88(1):101\u2013106","journal-title":"Circulation"},{"issue":"2","key":"3912_CR2","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1039\/D1BM01454D","volume":"10","author":"E \u00c1lvarez-Benedicto","year":"2022","unstructured":"\u00c1lvarez-Benedicto E, Farbiak L, Ram\u00edrez MM, Wang X, Johnson LT, Mian O, Siegwart DJ (2022) Optimization of phospholipid chemistry for improved lipid nanoparticle (LNP) delivery of messenger RNA (mRNA). Biomater Sci 10(2):549\u2013559","journal-title":"Biomater Sci"},{"issue":"2","key":"3912_CR3","doi-asserted-by":"publisher","first-page":"641","DOI":"10.4049\/jimmunol.119.2.641","volume":"119","author":"M-A Bach","year":"1977","unstructured":"Bach M-A (1977) Lymphocyte-mediated cytotoxicity: effects of ageing, adult thymectomy and thymic factor. J Immunol 119(2):641\u2013647","journal-title":"J Immunol"},{"key":"3912_CR4","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.omtn.2019.02.018","volume":"15","author":"M Baiersd\u00f6rfer","year":"2019","unstructured":"Baiersd\u00f6rfer M, Boros G, Muramatsu H, Mahiny A, Vlatkovic I, Sahin U, Karik\u00f3 K (2019) A facile method for the removal of dsRNA contaminant from in vitro-transcribed mRNA. Mol Ther Nucleic Acids 15:26\u201335. https:\/\/doi.org\/10.1016\/j.omtn.2019.02.018","journal-title":"Mol Ther Nucleic Acids"},{"issue":"5","key":"3912_CR5","first-page":"421","volume":"11","author":"B Bodey","year":"1997","unstructured":"Bodey B, Bodey B Jr, Siegel S, Kaiser H (1997) Involution of the mammalian thymus, one of the leading regulators of aging. In Vivo (Athens, Greece) 11(5):421\u2013440","journal-title":"In Vivo (Athens, Greece)"},{"issue":"6","key":"3912_CR6","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1161\/CIRCULATIONAHA.121.056135","volume":"144","author":"B Bozkurt","year":"2021","unstructured":"Bozkurt B, Kamat I, Hotez PJ (2021) Myocarditis with COVID-19 mRNA vaccines. Circulation 144(6):471\u2013484","journal-title":"Circulation"},{"key":"3912_CR7","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.15035","author":"S Brito","year":"2021","unstructured":"Brito S, Ferreira N, Mateus S, Bernardo M, Pinto B, Louren\u00e7o A, Grenho F (2021) A case of autoimmune hemolytic anemia following COVID-19 messenger ribonucleic acid vaccination. Cureus. https:\/\/doi.org\/10.7759\/cureus.15035","journal-title":"Cureus"},{"issue":"3","key":"3912_CR8","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1002\/jat.4548","volume":"44","author":"K Broudic","year":"2023","unstructured":"Broudic K, Laurent S, Perkov V, Simon C, Garinot M, Truchot N, D\u00e9sert P (2023) Nonclinical safety assessment of an mRNA COVID-19 vaccine candidate following repeated administrations and biodistribution. J Appl Toxicol 44(3):371\u2013390","journal-title":"J Appl Toxicol"},{"issue":"2","key":"3912_CR9","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/S0002-9149(01)02206-8","volume":"89","author":"RJ Carlson","year":"2002","unstructured":"Carlson RJ, Navone A, McConnell JP, Burritt M, Castle MC, Grill D, Jaffe AS (2002) Effect of myocardial ischemia on cardiac troponin I and T. Am J Cardiol 89(2):224\u2013226","journal-title":"Am J Cardiol"},{"issue":"11","key":"3912_CR10","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1038\/s41573-021-00283-5","volume":"20","author":"N Chaudhary","year":"2021","unstructured":"Chaudhary N, Weissman D, Whitehead KA (2021ba) mRNA vaccines for infectious diseases: principles, delivery and clinical translation. Nat Rev Drug Discov 20(11):817\u2013838. https:\/\/doi.org\/10.1038\/s41573-021-00283-5","journal-title":"Nat Rev Drug Discov"},{"key":"3912_CR11","doi-asserted-by":"publisher","first-page":"2893","DOI":"10.2147\/IJN.S363990","volume":"17","author":"H Chen","year":"2022","unstructured":"Chen H, Ren X, Xu S, Zhang D, Han T (2022) Optimization of lipid nanoformulations for effective mRNA delivery. Int J Nanomed 17:2893\u20132905","journal-title":"Int J Nanomed"},{"issue":"1","key":"3912_CR12","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1177\/10915818221138781","volume":"42","author":"DA Donahue","year":"2023","unstructured":"Donahue DA, Ballesteros C, Maruggi G, Glover C, Ringenberg MA, Marquis M, Stokes AH (2023) Nonclinical safety assessment of lipid nanoparticle-and emulsion-based self-amplifying mRNA vaccines in rats. Int J Toxicol 42(1):37\u201349","journal-title":"Int J Toxicol"},{"issue":"1","key":"3912_CR13","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/S0278-6915(00)00107-1","volume":"39","author":"P Dortant","year":"2001","unstructured":"Dortant P, Peters-Volleberg G, Van Loveren H, Marquardt R, Speijers G (2001) Age-related differences in the toxicity of ochratoxin A in female rats. Food Chem Toxicol 39(1):55\u201365","journal-title":"Food Chem Toxicol"},{"issue":"19","key":"3912_CR14","doi-asserted-by":"publisher","first-page":"1774","DOI":"10.1056\/NEJMoa2113017","volume":"385","author":"HM El Sahly","year":"2021","unstructured":"El Sahly HM, Baden LR, Essink B, Doblecki-Lewis S, Martin JM, Anderson EJ, Fichtenbaum CJ (2021) Efficacy of the mRNA-1273 SARS-CoV-2 vaccine at completion of blinded phase. N Engl J Med 385(19):1774\u20131785","journal-title":"N Engl J Med"},{"issue":"11","key":"3912_CR15","doi-asserted-by":"publisher","first-page":"4774","DOI":"10.1021\/acs.nanolett.1c01284","volume":"21","author":"U Elia","year":"2021","unstructured":"Elia U, Rotem S, Bar-Haim E, Ramishetti S, Naidu GS, Gur D, Alcalay R (2021) Lipid nanoparticle RBD-hFc mRNA vaccine protects hACE2 transgenic mice against a lethal SARS-CoV-2 infection. Nano Lett 21(11):4774\u20134779","journal-title":"Nano Lett"},{"issue":"48","key":"3912_CR16","doi-asserted-by":"publisher","first-page":"28256","DOI":"10.1039\/D0CP05111J","volume":"22","author":"I Ermilova","year":"2020","unstructured":"Ermilova I, Swenson J (2020) DOPC versus DOPE as a helper lipid for gene-therapies: molecular dynamics simulations with DLin-MC3-DMA. Phys Chem Chem Phys 22(48):28256\u201328268","journal-title":"Phys Chem Chem Phys"},{"key":"3912_CR17","unstructured":"FDA (2022) Summary basis for regulatory action. BLA\/NDA STN : STN 125752\/0"},{"key":"3912_CR18","unstructured":"FDA (2022) Toxicology review of COVID-19 vaccine (BNT162, PF-07302048, Final Report), BLA 125742"},{"issue":"1","key":"3912_CR19","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1093\/ajcp\/110.1.70","volume":"110","author":"Y-J Feng","year":"1998","unstructured":"Feng Y-J, Chen C, Fallon JT, Lai T, Chen L, Knibbs DR, Wu AH (1998) Comparison of cardiac troponin I, creatine kinase-MB, and myoglobin for detection of acute ischemic myocardial injury in a swine model. Am J Clin Pathol 110(1):70\u201377","journal-title":"Am J Clin Pathol"},{"key":"3912_CR20","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/s00281-018-0726-5","volume":"41","author":"S Fischinger","year":"2019","unstructured":"Fischinger S, Boudreau CM, Butler AL, Streeck H, Alter G (2019) Sex differences in vaccine-induced humoral immunity. Semin Immunopathol 41:239\u2013249","journal-title":"Semin Immunopathol"},{"issue":"9423","key":"3912_CR21","doi-asserted-by":"publisher","first-page":"1802","DOI":"10.1016\/S0140-6736(04)16308-3","volume":"363","author":"ME Franks","year":"2004","unstructured":"Franks ME, Macpherson GR, Figg WD (2004) Thalidomide. The Lancet 363(9423):1802\u20131811","journal-title":"The Lancet"},{"issue":"11","key":"3912_CR22","doi-asserted-by":"publisher","first-page":"3267","DOI":"10.1111\/trf.16672","volume":"61","author":"SR Gadi","year":"2021","unstructured":"Gadi SR, Brunker PA, Al-Samkari H, Sykes DB, Saff RR, Lo J, Leaf RK (2021) Severe autoimmune hemolytic anemia following receipt of SARS-CoV-2 mRNA vaccine. Transfusion 61(11):3267\u20133271","journal-title":"Transfusion"},{"key":"3912_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2021.108818","volume":"230","author":"M Garc\u00eda-Grimshaw","year":"2021","unstructured":"Garc\u00eda-Grimshaw M, Michel-Ch\u00e1vez A, Vera-Zertuche JM, Galnares-Olalde JA, Hern\u00e1ndez-Vanegas LE, Figueroa-Cucurachi M, Arauz A (2021) Guillain-Barr\u00e9 syndrome is infrequent among recipients of the BNT162b2 mRNA COVID-19 vaccine. Clin Immunol 230:108818","journal-title":"Clin Immunol"},{"issue":"1","key":"3912_CR24","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1038\/s41746-022-00711-9","volume":"5","author":"EA Gibson","year":"2022","unstructured":"Gibson EA, Li H, Fruh V, Gabra M, Asokan G, Jukic AMZ, Onnela J-P (2022) COVID-19 vaccination and menstrual cycle length in the Apple Women\u2019s Health Study. Npj Digit Med 5(1):165","journal-title":"Npj Digit Med"},{"key":"3912_CR25","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111953","volume":"142","author":"JT Granados-Riveron","year":"2021","unstructured":"Granados-Riveron JT, Aquino-Jarquin G (2021) Engineering of the current nucleoside-modified mRNA-LNP vaccines against SARS-CoV-2. Biomed Pharmacother 142:111953","journal-title":"Biomed Pharmacother"},{"key":"3912_CR26","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2024.114219","volume":"197","author":"CH Gregersen","year":"2024","unstructured":"Gregersen CH, Mearraoui R, S\u00f8gaard PP, Clergeaud G, Petersson K, Urquhart AJ, Simonsen JB (2024) Lipid nanoparticles containing labile PEG-lipids transfect primary human skin cells more efficiently in the presence of apoE. Eur J Pharm Biopharm 197:114219","journal-title":"Eur J Pharm Biopharm"},{"key":"3912_CR27","doi-asserted-by":"crossref","unstructured":"Greinacher A, Selleng K, Mayerle J, Palankar R, Wesche J, Reiche S, Thiele T (2021) Anti-SARS-CoV-2 spike protein and anti-platelet factor 4 antibody responses induced by COVID-19 disease and ChAdOx1 nCov-19 vaccination","DOI":"10.21203\/rs.3.rs-404769\/v1"},{"issue":"25","key":"3912_CR28","first-page":"4938","volume":"120","author":"L Grimaldi-Bensouda","year":"2012","unstructured":"Grimaldi-Bensouda L, Michel M, Aubrun E, Leighton P, Viallard JF, Adoue D, Godeau B (2012) A case-control study to assess the risk of immune thrombocytopenia associated with vaccines. Blood, J Am Soc Hematol 120(25):4938\u20134944","journal-title":"Blood, J Am Soc Hematol"},{"issue":"7","key":"3912_CR29","doi-asserted-by":"publisher","first-page":"5167","DOI":"10.1021\/acs.nanolett.0c00596","volume":"20","author":"KA Hajj","year":"2020","unstructured":"Hajj KA, Melamed JR, Chaudhary N, Lamson NG, Ball RL, Yerneni SS, Whitehead KA (2020) A potent branched-tail lipid nanoparticle enables multiplexed mRNA delivery and gene editing in vivo. Nano Lett 20(7):5167\u20135175","journal-title":"Nano Lett"},{"issue":"1","key":"3912_CR30","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1038\/s41541-023-00719-6","volume":"8","author":"R Hajjo","year":"2023","unstructured":"Hajjo R, Momani E, Sabbah DA, Baker N, Tropsha A (2023) Identifying a causal link between prolactin signaling pathways and COVID-19 vaccine-induced menstrual changes. Npj Vaccines 8(1):129","journal-title":"Npj Vaccines"},{"key":"3912_CR31","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.thromres.2017.07.031","volume":"158","author":"KE Hally","year":"2017","unstructured":"Hally KE, La Flamme AC, Larsen PD, Harding SA (2017) Platelet Toll-like receptor (TLR) expression and TLR-mediated platelet activation in acute myocardial infarction. Thromb Res 158:8\u201315","journal-title":"Thromb Res"},{"key":"3912_CR32","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2016-0124","author":"U Hamiel","year":"2016","unstructured":"Hamiel U, Kventsel I, Youngster I (2016) Recurrent immune thrombocytopenia after influenza vaccination: a case report. Pediatrics. https:\/\/doi.org\/10.1542\/peds.2016-0124","journal-title":"Pediatrics"},{"issue":"4","key":"3912_CR33","doi-asserted-by":"publisher","first-page":"e228879","DOI":"10.1001\/jamanetworkopen.2022.8879","volume":"5","author":"KE Hanson","year":"2022","unstructured":"Hanson KE, Goddard K, Lewis N, Fireman B, Myers TR, Bakshi N, Xu S (2022) Incidence of Guillain-Barr\u00e9 syndrome after COVID-19 vaccination in the vaccine safety datalink. JAMA Netw Open 5(4):e228879\u2013e228879","journal-title":"JAMA Netw Open"},{"issue":"15","key":"3912_CR34","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1161\/CIRCULATIONAHA.115.020143","volume":"133","author":"O Henri","year":"2016","unstructured":"Henri O, Pouehe C, Houssari M, Galas L, Nicol L, Edwards-L\u00e9vy F, Banquet S (2016) Selective stimulation of cardiac lymphangiogenesis reduces myocardial edema and fibrosis leading to improved cardiac function following myocardial infarction. Circulation 133(15):1484\u20131497","journal-title":"Circulation"},{"issue":"12","key":"3912_CR35","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1038\/s41578-021-00358-0","volume":"6","author":"X Hou","year":"2021","unstructured":"Hou X, Zaks T, Langer R, Dong Y (2021) Lipid nanoparticles for mRNA delivery. Nat Rev Mater 6(12):1078\u20131094","journal-title":"Nat Rev Mater"},{"issue":"1","key":"3912_CR36","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1038\/s41467-021-21037-2","volume":"12","author":"Q Huang","year":"2021","unstructured":"Huang Q, Ji K, Tian S, Wang F, Huang B, Tong Z, Tan W (2021) A single-dose mRNA vaccine provides a long-term protection for hACE2 transgenic mice from SARS-CoV-2. Nat Commun 12(1):776","journal-title":"Nat Commun"},{"key":"3912_CR37","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1016\/j.ijid.2021.04.047","volume":"106","author":"RA Kadali","year":"2021","unstructured":"Kadali RA, Janagama R, Peruru S, Malayala SV (2021) Side effects of BNT162b2 mRNA COVID-19 vaccine: a randomized, cross-sectional study with detailed self-reported symptoms from healthcare workers. Int J Infect Dis 106:376\u2013381","journal-title":"Int J Infect Dis"},{"issue":"11","key":"3912_CR38","doi-asserted-by":"publisher","first-page":"7300","DOI":"10.1021\/acs.nanolett.5b02497","volume":"15","author":"KJ Kauffman","year":"2015","unstructured":"Kauffman KJ, Dorkin JR, Yang JH, Heartlein MW, DeRosa F, Mir FF, Anderson DG (2015) Optimization of lipid nanoparticle formulations for mRNA delivery in vivo with fractional factorial and definitive screening designs. Nano Lett 15(11):7300\u20137306","journal-title":"Nano Lett"},{"issue":"6","key":"3912_CR39","doi-asserted-by":"publisher","first-page":"711","DOI":"10.2131\/jts.41.711","volume":"41","author":"H-R Kim","year":"2016","unstructured":"Kim H-R, Hwang G-W, Naganuma A, Chung K-H (2016) Adverse health effects of humidifier disinfectants in Korea: lung toxicity of polyhexamethylene guanidine phosphate. J Toxicol Sci 41(6):711\u2013717","journal-title":"J Toxicol Sci"},{"issue":"10","key":"3912_CR40","doi-asserted-by":"publisher","first-page":"1196","DOI":"10.1001\/jamacardio.2021.2828","volume":"6","author":"HW Kim","year":"2021","unstructured":"Kim HW, Jenista ER, Wendell DC, Azevedo CF, Campbell MJ, Darty SN, Kim RJ (2021) Patients with acute myocarditis following mRNA COVID-19 vaccination. JAMA Cardiol 6(10):1196\u20131201","journal-title":"JAMA Cardiol"},{"issue":"1","key":"3912_CR41","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1007\/s00418-006-0226-x","volume":"127","author":"R Kivel\u00e4","year":"2007","unstructured":"Kivel\u00e4 R, Havas E, Vihko V (2007) Localisation of lymphatic vessels and vascular endothelial growth factors-C and-D in human and mouse skeletal muscle with immunohistochemistry. Histochem Cell Biol 127(1):31\u201340","journal-title":"Histochem Cell Biol"},{"issue":"1","key":"3912_CR42","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1093\/trstmh\/tru167","volume":"109","author":"SL Klein","year":"2015","unstructured":"Klein SL, Marriott I, Fish EN (2015) Sex-based differences in immune function and responses to vaccination. Trans R Soc Trop Med Hyg 109(1):9\u201315","journal-title":"Trans R Soc Trop Med Hyg"},{"issue":"7554","key":"3912_CR43","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1038\/nature14483","volume":"522","author":"L Klotz","year":"2015","unstructured":"Klotz L, Norman S, Vieira JM, Masters M, Rohling M, Dub\u00e9 KN, Riley PR (2015) Cardiac lymphatics are heterogeneous in origin and respond to injury. Nature 522(7554):62\u201367","journal-title":"Nature"},{"issue":"5","key":"3912_CR44","first-page":"791","volume":"124","author":"M Koupenova","year":"2014","unstructured":"Koupenova M, Vitseva O, MacKay CR, Beaulieu LM, Benjamin EJ, Mick E, Freedman JE (2014) Platelet-TLR7 mediates host survival and platelet count during viral infection in the absence of platelet-dependent thrombosis. Blood, J Am Soc Hematol 124(5):791\u2013802","journal-title":"Blood, J Am Soc Hematol"},{"key":"3912_CR45","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.74974.sa0","author":"E Kowarz","year":"2022","unstructured":"Kowarz E, Krutzke L, K\u00fclp M, Streb P, Larghero P, Reis J, Marschalek R (2022) Vaccine-induced COVID-19 mimicry syndrome. Elife. https:\/\/doi.org\/10.7554\/eLife.74974.sa0","journal-title":"Elife"},{"issue":"3","key":"3912_CR46","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/S1473-3099(21)00677-0","volume":"22","author":"PG Kremsner","year":"2022","unstructured":"Kremsner PG, Guerrero RAA, Arana-Arri E, Martinez GJA, Bonten M, Chandler R, Gabor JJ (2022) Efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate in ten countries in Europe and Latin America (HERALD): a randomised, observer-blinded, placebo-controlled, phase 2b\/3 trial. Lancet Infect Dis 22(3):329\u2013340","journal-title":"Lancet Infect Dis"},{"issue":"6525","key":"3912_CR47","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1126\/science.aay3638","volume":"371","author":"C Krienke","year":"2021","unstructured":"Krienke C, Kolb L, Diken E, Streuber M, Kirchhoff S, Bukur T, Petschenka J (2021) A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis. Science 371(6525):145\u2013153","journal-title":"Science"},{"issue":"5","key":"3912_CR48","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1097\/01.mbc.0000469521.23628.2d","volume":"26","author":"M Krishnegowda","year":"2015","unstructured":"Krishnegowda M, Rajashekaraiah V (2015) Platelet disorders: an overview. Blood Coag Fibrinol 26(5):479\u2013491","journal-title":"Blood Coag Fibrinol"},{"key":"3912_CR49","first-page":"25","volume":"1","author":"CF Kuper","year":"1992","unstructured":"Kuper CF, Beems RB, Bruijntjes JP, Schuurman H-J, Vos JG (1992) Normal development, growth, and aging of the thymus. Pathobiol Aging Rat 1:25\u201348","journal-title":"Pathobiol Aging Rat"},{"issue":"4","key":"3912_CR50","doi-asserted-by":"publisher","first-page":"724","DOI":"10.1016\/j.immuni.2020.07.019","volume":"53","author":"D Laczk\u00f3","year":"2020","unstructured":"Laczk\u00f3 D, Hogan MJ, Toulmin SA, Hicks P, Lederer K, Gaudette BT, Oguin TH (2020) A single immunization with nucleoside-modified mRNA vaccines elicits strong cellular and humoral immune responses against SARS-CoV-2 in mice. Immunity 53(4):724-732.e727","journal-title":"Immunity"},{"issue":"8","key":"3912_CR51","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1080\/14760584.2021.1949294","volume":"20","author":"C-C Lai","year":"2021","unstructured":"Lai C-C, Ko W-C, Chen C-J, Chen P-Y, Huang Y-C, Lee P-I, Hsueh P-R (2021) COVID-19 vaccines and thrombosis with thrombocytopenia syndrome. Expert Rev Vaccines 20(8):1027\u20131035","journal-title":"Expert Rev Vaccines"},{"issue":"6","key":"3912_CR52","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1161\/CIRCULATIONAHA.121.055913","volume":"144","author":"KF Larson","year":"2021","unstructured":"Larson KF, Ammirati E, Adler ED, Cooper LT Jr, Hong KN, Saponara G, Cavalotti C (2021) Myocarditis after BNT162b2 and mRNA-1273 vaccination. Circulation 144(6):506\u2013508","journal-title":"Circulation"},{"issue":"10","key":"3912_CR53","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1038\/s12276-023-01086-x","volume":"55","author":"Y Lee","year":"2023","unstructured":"Lee Y, Jeong M, Park J, Jung H, Lee H (2023) Immunogenicity of lipid nanoparticles and its impact on the efficacy of mRNA vaccines and therapeutics. Exp Mol Med 55(10):2085\u20132096","journal-title":"Exp Mol Med"},{"issue":"11","key":"3912_CR54","doi-asserted-by":"publisher","first-page":"1933","DOI":"10.1093\/cid\/ciab707","volume":"74","author":"C Li","year":"2022","unstructured":"Li C, Chen Y, Zhao Y, Lung DC, Ye Z, Song W, Yip CC-Y (2022) Intravenous injection of coronavirus disease 2019 (COVID-19) mRNA vaccine can induce acute myopericarditis in mouse model. Clin Infect Dis 74(11):1933\u20131950","journal-title":"Clin Infect Dis"},{"issue":"8","key":"3912_CR55","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1384","volume":"13","author":"Y Li","year":"2023","unstructured":"Li Y, Wang M, Peng X, Yang Y, Chen Q, Liu J, Liao Z (2023) mRNA vaccine in cancer therapy: current advance and future outlook. Clin Transl Med 13(8):e1384","journal-title":"Clin Transl Med"},{"issue":"2","key":"3912_CR56","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/ni1033","volume":"5","author":"PJ Linton","year":"2004","unstructured":"Linton PJ, Dorshkind K (2004) Age-related changes in lymphocyte development and function. Nat Immunol 5(2):133\u2013139","journal-title":"Nat Immunol"},{"issue":"2","key":"3912_CR57","doi-asserted-by":"publisher","first-page":"140","DOI":"10.3109\/10520295.2011.577755","volume":"87","author":"L Liu","year":"2012","unstructured":"Liu L, Du X, Wang Z, Wu B, Jin M, Xin B, Bai Z (2012) A simplified intrathymic injection technique for mice. Biotech Histochem 87(2):140\u2013147","journal-title":"Biotech Histochem"},{"issue":"5","key":"3912_CR58","doi-asserted-by":"publisher","first-page":"1864","DOI":"10.1073\/pnas.0910603106","volume":"107","author":"KT Love","year":"2010","unstructured":"Love KT, Mahon KP, Levins CG, Whitehead KA, Querbes W, Dorkin JR, Racie T (2010) Lipid-like materials for low-dose, in vivo gene silencing. Proc Natl Acad Sci 107(5):1864\u20131869","journal-title":"Proc Natl Acad Sci"},{"issue":"14","key":"3912_CR59","doi-asserted-by":"publisher","first-page":"5130","DOI":"10.3390\/ijms21145130","volume":"21","author":"K Lundstrom","year":"2020","unstructured":"Lundstrom K (2020) Self-amplifying RNA viruses as RNA vaccines. Int J Mol Sci 21(14):5130","journal-title":"Int J Mol Sci"},{"key":"3912_CR60","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.887402","volume":"13","author":"J McCright","year":"2022","unstructured":"McCright J, Naiknavare R, Yarmovsky J, Maisel K (2022) Targeting lymphatics for nanoparticle drug delivery. Front Pharmacol 13:887402","journal-title":"Front Pharmacol"},{"key":"3912_CR61","unstructured":"Merchant H (2021) COVID-19 post-vaccine menorrhagia, metrorrhagia or postmenopausal bleeding and potential risk of vaccine-induced thrombocytopenia in women. The BMJ"},{"issue":"1","key":"3912_CR62","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12943-021-01335-5","volume":"20","author":"L Miao","year":"2021","unstructured":"Miao L, Zhang Y, Huang L (2021) mRNA vaccine for cancer immunotherapy. Mol Cancer 20(1):1\u201323","journal-title":"Mol Cancer"},{"key":"3912_CR63","unstructured":"Moderna E (2021) Assessment report COVID-19 vaccine moderna. Procedure No. Retrieved from"},{"issue":"3","key":"3912_CR64","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/S0002-9149(00)01382-5","volume":"87","author":"G Neumayr","year":"2001","unstructured":"Neumayr G, Gaenzer H, Pfister R, Sturm W, Schwarzacher SP, Eibl G, Hoertnagl H (2001) Plasma levels of cardiac troponin I after prolonged strenuous endurance exercise. Am J Cardiol 87(3):369\u2013371","journal-title":"Am J Cardiol"},{"issue":"50","key":"3912_CR65","doi-asserted-by":"publisher","first-page":"1922","DOI":"10.15585\/mmwr.mm6950e2","volume":"69","author":"SE Oliver","year":"2020","unstructured":"Oliver SE, Gargano JW, Marin M, Wallace M, Curran KG, Chamberland M, Mbaeyi S (2020) The advisory committee on immunization practices\u2019 interim recommendation for use of Pfizer-BioNTech COVID-19 vaccine\u2014United States, December 2020. Morb Mortal Wkly Rep 69(50):1922","journal-title":"Morb Mortal Wkly Rep"},{"issue":"3","key":"3912_CR66","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.tox.2007.11.021","volume":"245","author":"J Ozer","year":"2008","unstructured":"Ozer J, Ratner M, Shaw M, Bailey W, Schomaker S (2008) The current state of serum biomarkers of hepatotoxicity. Toxicology 245(3):194\u2013205","journal-title":"Toxicology"},{"issue":"1","key":"3912_CR67","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1161\/CIRCRESAHA.112.274241","volume":"112","author":"S Panigrahi","year":"2013","unstructured":"Panigrahi S, Ma Y, Hong L, Gao D, West XZ, Salomon RG, Podrez EA (2013) Engagement of platelet toll-like receptor 9 by novel endogenous ligands promotes platelet hyperreactivity and thrombosis. Circ Res 112(1):103\u2013112","journal-title":"Circ Res"},{"key":"3912_CR68","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/978-1-4939-6481-9_6","volume-title":"RNA vaccines: methods and protocols","author":"N Pardi","year":"2017","unstructured":"Pardi N, Weissman D (2017) Nucleoside modified mRNA vaccines for infectious diseases. RNA vaccines: methods and protocols. Humana Press, New York, pp 109\u2013121"},{"key":"3912_CR69","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.jconrel.2015.08.007","volume":"217","author":"N Pardi","year":"2015","unstructured":"Pardi N, Tuyishime S, Muramatsu H, Kariko K, Mui BL, Tam YK, Weissman D (2015) Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes. J Control Release 217:345\u2013351","journal-title":"J Control Release"},{"issue":"1","key":"3912_CR70","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1038\/s41541-023-00684-0","volume":"8","author":"HJ Park","year":"2023","unstructured":"Park HJ, Bang YJ, Kwon SP, Kwak W, Park SI, Roh G, Nam JH (2023) Analyzing immune responses to varied mRNA and protein vaccine sequences. Npj Vaccines 8(1):84. https:\/\/doi.org\/10.1038\/s41541-023-00684-0","journal-title":"Npj Vaccines"},{"key":"3912_CR71","first-page":"e932899","volume":"27","author":"DV Parums","year":"2021","unstructured":"Parums DV (2021) SARS-CoV-2 mRNA vaccines and the possible mechanism of vaccine-induced immune thrombotic thrombocytopenia (VITT). Med Sci Monit: Int Med J Exp Clin Res 27:e932899\u2013e932891","journal-title":"Med Sci Monit: Int Med J Exp Clin Res"},{"issue":"12","key":"3912_CR72","doi-asserted-by":"publisher","first-page":"3348","DOI":"10.1172\/JCI26891","volume":"115","author":"SR Patel","year":"2005","unstructured":"Patel SR, Hartwig JH, Italiano JE (2005) The biogenesis of platelets from megakaryocyte proplatelets. J Clin Investig 115(12):3348\u20133354","journal-title":"J Clin Investig"},{"issue":"24","key":"3912_CR73","doi-asserted-by":"publisher","first-page":"10025","DOI":"10.1021\/acs.nanolett.2c03741","volume":"22","author":"K Paunovska","year":"2022","unstructured":"Paunovska K, Da Silva Sanchez AJ, Lokugamage MP, Loughrey D, Echeverri ES, Cristian A, Dahlman JE (2022) The extent to which lipid nanoparticles require apolipoprotein E and low-density lipoprotein receptor for delivery changes with ionizable lipid structure. Nano Lett 22(24):10025\u201310033","journal-title":"Nano Lett"},{"key":"3912_CR74","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1007\/s12026-014-8597-x","volume":"60","author":"C Perricone","year":"2014","unstructured":"Perricone C, Ceccarelli F, Nesher G, Borella E, Odeh Q, Conti F, Valesini G (2014) Immune thrombocytopenic purpura (ITP) associated with vaccinations: a review of reported cases. Immunol Res 60:226\u2013235","journal-title":"Immunol Res"},{"issue":"10","key":"3912_CR75","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.3390\/ph14101049","volume":"14","author":"A Riad","year":"2021","unstructured":"Riad A, Pokorn\u00e1 A, Klugarov\u00e1 J, Antalov\u00e1 N, Kantorov\u00e1 L, Ko\u0161\u010d\u00edk M, Klugar M (2021) Side effects of mRNA-based COVID-19 vaccines among young adults (18\u201330 years old): an independent post-marketing study. Pharmaceuticals 14(10):1049","journal-title":"Pharmaceuticals"},{"issue":"3","key":"3912_CR76","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.ejheart.2004.01.003","volume":"6","author":"M Richards","year":"2004","unstructured":"Richards M, Troughton RW (2004) NT-proBNP in heart failure: therapy decisions and monitoring. Eur J Heart Fail 6(3):351\u2013354","journal-title":"Eur J Heart Fail"},{"issue":"7","key":"3912_CR77","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1016\/S0002-9149(99)00020-X","volume":"83","author":"N Rifai","year":"1999","unstructured":"Rifai N, Douglas PS, O\u2019Toole M, Rimm E, Ginsburg GS (1999) Cardiac troponin T and I, electrocardiographic wall motion analyses, and ejection fractions in athletes participating in the Hawaii Ironman Triathlon. Am J Cardiol 83(7):1085\u20131089","journal-title":"Am J Cardiol"},{"issue":"11","key":"3912_CR78","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1089\/hum.2005.16.1276","volume":"16","author":"J Rip","year":"2005","unstructured":"Rip J, Nierman MC, Sierts JA, Petersen W, Den Oever KV, Raalte DV, Dijkhuizen P (2005) Gene therapy for lipoprotein lipase deficiency: working toward clinical application. Hum Gene Ther 16(11):1276\u20131286","journal-title":"Hum Gene Ther"},{"issue":"2","key":"3912_CR79","doi-asserted-by":"publisher","first-page":"417","DOI":"10.3390\/vaccines11020417","volume":"11","author":"CM Rohde","year":"2023","unstructured":"Rohde CM, Lindemann C, Giovanelli M, Sellers RS, Diekmann J, Choudhary S, Muik A (2023) Toxicological assessments of a pandemic COVID-19 vaccine: demonstrating the suitability of a platform approach for mRNA vaccines. Vaccines 11(2):417","journal-title":"Vaccines"},{"issue":"8","key":"3912_CR80","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.7326\/L21-0244","volume":"174","author":"S Sangli","year":"2021","unstructured":"Sangli S, Virani A, Cheronis N, Vannatter B, Minich C, Noronha S, Kaplan RB (2021) Thrombosis with thrombocytopenia after the messenger RNA\u20131273 vaccine. Ann Intern Med 174(8):1480\u20131482","journal-title":"Ann Intern Med"},{"issue":"4","key":"3912_CR81","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/j.coi.2011.05.001","volume":"23","author":"D Sauce","year":"2011","unstructured":"Sauce D, Appay V (2011) Altered thymic activity in early life: how does it affect the immune system in young adults? Curr Opin Immunol 23(4):543\u2013548","journal-title":"Curr Opin Immunol"},{"issue":"4","key":"3912_CR82","doi-asserted-by":"publisher","first-page":"6709","DOI":"10.1021\/acsnano.0c10064","volume":"15","author":"F Sebastiani","year":"2021","unstructured":"Sebastiani F, Yanez Arteta M, Lerche M, Porcar L, Lang C, Bragg RA, Darwish T (2021) Apolipoprotein E binding drives structural and compositional rearrangement of mRNA-containing lipid nanoparticles. ACS Nano 15(4):6709\u20136722","journal-title":"ACS Nano"},{"issue":"2","key":"3912_CR83","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1177\/0300985817738095","volume":"55","author":"M Sedic","year":"2018","unstructured":"Sedic M, Senn JJ, Lynn A, Laska M, Smith M, Platz SJ, Jacquinet E (2018) Safety evaluation of lipid nanoparticle\u2013formulated modified mRNA in the sprague-dawley rat and cynomolgus monkey. Vet Pathol 55(2):341\u2013354","journal-title":"Vet Pathol"},{"issue":"6","key":"3912_CR84","doi-asserted-by":"publisher","first-page":"542","DOI":"10.30699\/jogcr.8.6.542","volume":"8","author":"M Seyfi-Ghale-Jogh","year":"2023","unstructured":"Seyfi-Ghale-Jogh M, Mehrali M, Rakhshanimehr R, Mohammadyari F, Safari E, Salehi-Shadkami M, Haryalchi K (2023) The importance of female reproductive changes in COVID-19 and vaccine administration: a narrative review. J Obstet, Gynecol Cancer Res 8(6):542\u2013548","journal-title":"J Obstet, Gynecol Cancer Res"},{"key":"3912_CR85","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1007\/s12291-013-0408-y","volume":"29","author":"U Sharma","year":"2014","unstructured":"Sharma U, Pal D, Prasad R (2014) Alkaline phosphatase: an overview. Indian J Clin Biochem 29:269\u2013278","journal-title":"Indian J Clin Biochem"},{"issue":"8","key":"3912_CR86","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.3390\/ph15081017","volume":"15","author":"R Shimosakai","year":"2022","unstructured":"Shimosakai R, Khalil IA, Kimura S, Harashima H (2022) mRNA-loaded lipid nanoparticles targeting immune cells in the spleen for use as cancer vaccines. Pharmaceuticals 15(8):1017","journal-title":"Pharmaceuticals"},{"issue":"2","key":"3912_CR87","doi-asserted-by":"publisher","first-page":"212","DOI":"10.3109\/17435390.2013.782076","volume":"8","author":"AH Silva","year":"2014","unstructured":"Silva AH, Locatelli C, Filippin-Monteiro FB, Zanetti-Ramos BG, Conte A, Creczynski-Pasa TB (2014) Solid lipid nanoparticles induced hematological changes and inflammatory response in mice. Nanotoxicology 8(2):212\u2013219","journal-title":"Nanotoxicology"},{"key":"3912_CR88","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2020.104648","volume":"113","author":"A Stokes","year":"2020","unstructured":"Stokes A, Pion J, Binazon O, Laffont B, Bigras M, Dubois G, Abdeljelil NB (2020) Nonclinical safety assessment of repeated administration and biodistribution of a novel rabies self-amplifying mRNA vaccine in rats. Regul Toxicol Pharmacol 113:104648","journal-title":"Regul Toxicol Pharmacol"},{"issue":"1","key":"3912_CR89","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1080\/14760584.2022.2002690","volume":"21","author":"C Switzer","year":"2022","unstructured":"Switzer C, Loeb M (2022) Evaluating the relationship between myocarditis and mRNA vaccination. Expert Rev Vaccines 21(1):83\u201389","journal-title":"Expert Rev Vaccines"},{"issue":"9","key":"3912_CR90","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1038\/mt.2015.103","volume":"23","author":"A Thess","year":"2015","unstructured":"Thess A, Grund S, Mui BL, Hope MJ, Baumhof P, Fotin-Mleczek M, Schlake T (2015) Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals. Mol Ther 23(9):1456\u20131464","journal-title":"Mol Ther"},{"issue":"2","key":"3912_CR91","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1261\/rna.048272.114","volume":"21","author":"Y Wang","year":"2015","unstructured":"Wang Y, Wang Z (2015) Efficient backsplicing produces translatable circular mRNAs. RNA 21(2):172\u2013179","journal-title":"RNA"},{"issue":"2","key":"3912_CR92","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.ejps.2009.06.008","volume":"38","author":"J-J Wang","year":"2009","unstructured":"Wang J-J, Liu K-S, Sung K, Tsai C-Y, Fang J-Y (2009) Lipid nanoparticles with different oil\/fatty ester ratios as carriers of buprenorphine and its prodrugs for injection. Eur J Pharm Sci 38(2):138\u2013146","journal-title":"Eur J Pharm Sci"},{"issue":"1","key":"3912_CR93","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1186\/s12929-023-00977-5","volume":"30","author":"Y-S Wang","year":"2023","unstructured":"Wang Y-S, Kumari M, Chen G-H, Hong M-H, Yuan JP-Y, Tsai J-L, Wu H-C (2023) mRNA-based vaccines and therapeutics: an in-depth survey of current and upcoming clinical applications. J Biomed Sci 30(1):84","journal-title":"J Biomed Sci"},{"key":"3912_CR94","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2020.107534","volume":"40","author":"Y Weng","year":"2020","unstructured":"Weng Y, Li C, Yang T, Hu B, Zhang M, Guo S, Huang Y (2020) The challenge and prospect of mRNA therapeutics landscape. Biotechnol Adv 40:107534","journal-title":"Biotechnol Adv"},{"issue":"1","key":"3912_CR95","doi-asserted-by":"publisher","first-page":"4277","DOI":"10.1038\/ncomms5277","volume":"5","author":"KA Whitehead","year":"2014","unstructured":"Whitehead KA, Dorkin JR, Vegas AJ, Chang PH, Veiseh O, Matthews J, Yesilyurt V (2014) Degradable lipid nanoparticles with predictable in vivo siRNA delivery activity. Nat Commun 5(1):4277","journal-title":"Nat Commun"},{"key":"3912_CR96","unstructured":"WHO (2005) Guidelines on nonclinical evaluation of vaccines, Technical Report Series, Annex 1"},{"key":"3912_CR97","unstructured":"WHO (2013) Guidelines on the nonclinical evaluation of vaccine adjuvants and adjuvanted vaccines. WHO Technical Report Series, TRS 987, Annex 2"},{"key":"3912_CR98","unstructured":"WHO (2021) Evaluation of the quality, safety and efficacy of messenger RNA vaccines for the prevention of infectious diseases: regulatory considerations, Technical document, Annex 3"},{"issue":"2","key":"3912_CR99","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1166\/jnn.2016.11667","volume":"16","author":"E Winter","year":"2016","unstructured":"Winter E, Pizzol CD, Locatelli C, Crezkynski-Pasa TB (2016) Development and evaluation of lipid nanoparticles for drug delivery: Study of toxicity in vitro and in vivo. J Nanosci Nanotechnol 16(2):1321\u20131330","journal-title":"J Nanosci Nanotechnol"},{"issue":"2","key":"3912_CR100","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/S0009-8981(99)00078-9","volume":"284","author":"AH Wu","year":"1999","unstructured":"Wu AH, Ford L (1999) Release of cardiac troponin in acute coronary syndromes: ischemia or necrosis? Clin Chim Acta 284(2):161\u2013174","journal-title":"Clin Chim Acta"},{"issue":"1","key":"3912_CR101","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.bbrc.2004.12.137","volume":"328","author":"X Yan","year":"2005","unstructured":"Yan X, Kuipers F, Havekes LM, Havinga R, Dontje B, Poelstra K, Kamps JA (2005) The role of apolipoprotein E in the elimination of liposomes from blood by hepatocytes in the mouse. Biochem Biophys Res Commun 328(1):57\u201362","journal-title":"Biochem Biophys Res Commun"},{"issue":"630","key":"3912_CR102","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abm3302","volume":"14","author":"B Ying","year":"2021","unstructured":"Ying B, Whitener B, VanBlargan LA, Hassan AO, Shrihari S, Liang C-Y, Kafai NM (2021) Protective activity of mRNA vaccines against ancestral and variant SARS-CoV-2 strains. Sci Transl Med 14(630):eabm3302","journal-title":"Sci Transl Med"},{"issue":"5","key":"3912_CR103","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1016\/j.cell.2020.07.024","volume":"182","author":"NN Zhang","year":"2020","unstructured":"Zhang NN, Li XF, Deng YQ, Zhao H, Huang YJ, Yang G, Qin CF (2020a) A thermostable mRNA vaccine against COVID-19. Cell 182(5):1271-1283.e1216. https:\/\/doi.org\/10.1016\/j.cell.2020.07.024","journal-title":"Cell"}],"container-title":["Archives of Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-024-03912-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00204-024-03912-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00204-024-03912-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T01:35:35Z","timestamp":1738114535000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00204-024-03912-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,10]]},"references-count":103,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["3912"],"URL":"https:\/\/doi.org\/10.1007\/s00204-024-03912-1","relation":{},"ISSN":["0340-5761","1432-0738"],"issn-type":[{"value":"0340-5761","type":"print"},{"value":"1432-0738","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,10]]},"assertion":[{"value":"10 September 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 November 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 December 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All authors declare that they have no conflicts of interest concerning the publication of this paper.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}