{"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":1792515593060,"version":"4.5.0"},"reference-count":60,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100003569","name":"Korea Ministry of Food and Drug Safety","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003569","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Toxicology Letters"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1016\/j.toxlet.2026.111941","type":"journal-article","created":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T16:14:31Z","timestamp":1781453671000},"page":"111941","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":3,"special_numbering":"C","title":["Nonclinical safety evaluation strategies for mRNA\/LNPs platform agents: Evidence from comprehensive animal toxicity studies"],"prefix":"10.1016","volume":"422","author":[{"given":"Jae-Hun","family":"Ahn","sequence":"first","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":"Jooil","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jina","family":"Kwak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Euna","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gahyun","family":"Roh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seo-Hyeon","family":"Bae","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo-Yeon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Il Kwon","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jisun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo-Jung","family":"Park","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":"Ji-Eun","family":"Kim","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"}]},{"given":"Byeong-Cheol","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.toxlet.2026.111941_bib1","unstructured":"Administration U.S.Fa.D.. Summary Basis for Regulatory Action [COVID-19 Vaccine, mRNA, COMIRNATY], [STN BL 125742]. U.S. Food and Drug Administration; 2021."},{"key":"10.1016\/j.toxlet.2026.111941_bib2","unstructured":"Agency, E.M., 2021. Adapting COVID-19 vaccines to SARS-CoV-2 variants: guidance for vaccine manufacturers. European Medicines Agency."},{"key":"10.1016\/j.toxlet.2026.111941_bib3","unstructured":"Agency, E.M., 2021. Assessment report [COVID-19 mRNA vaccine (nucleoside-modified)], Procedure No. EMEA\/H\/C\/005735\/0000. European Medicines Agency."},{"issue":"2","key":"10.1016\/j.toxlet.2026.111941_bib4","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1007\/s00204-024-03912-1","article-title":"Impact of administration routes and dose frequency on the toxicology of SARS-CoV-2 mRNA vaccines in mice model","volume":"99","author":"Ahn","year":"2025","journal-title":"Arch. Toxicol."},{"issue":"824","key":"10.1016\/j.toxlet.2026.111941_bib5","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.adz2276","article-title":"Incorporation of 5-methylcytidine alleviates RIG-I\u2013mediated innate immune responses to a self-amplifying RNA vaccine","volume":"17","author":"Akahata","year":"2025","journal-title":"Sci. Transl. Med."},{"issue":"8","key":"10.1016\/j.toxlet.2026.111941_bib6","article-title":"Rational design of lipid nanoparticles for enhanced mRNA vaccine delivery via machine learning","volume":"21","author":"Bae","year":"2025","journal-title":"Small"},{"key":"10.1016\/j.toxlet.2026.111941_bib7","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.omtn.2019.02.018","article-title":"A facile method for the removal of dsRNA contaminant from in vitro-transcribed mRNA","volume":"15","author":"Baiersd\u00f6rfer","year":"2019","journal-title":"Mol. Ther. Nucleic Acids"},{"issue":"1","key":"10.1016\/j.toxlet.2026.111941_bib8","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.yrtph.2015.07.019","article-title":"Nonclinical safety testing of biopharmaceuticals\u2013addressing current challenges of these novel and emerging therapies","volume":"73","author":"Brennan","year":"2015","journal-title":"Regul. Toxicol. Pharmacol."},{"issue":"1","key":"10.1016\/j.toxlet.2026.111941_bib9","doi-asserted-by":"crossref","first-page":"H1","DOI":"10.1152\/ajpheart.00093.2022","article-title":"Myocardial injury, troponin release, and cardiomyocyte death in brief ischemia, failure, and ventricular remodeling","volume":"323","author":"Canty","year":"2022","journal-title":"Am. J. Physiol. -Heart Circ. Physiol."},{"issue":"2","key":"10.1016\/j.toxlet.2026.111941_bib10","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/S0002-9149(01)02206-8","article-title":"Effect of myocardial ischemia on cardiac troponin I and T","volume":"89","author":"Carlson","year":"2002","journal-title":"Am. J. Cardiol."},{"issue":"11","key":"10.1016\/j.toxlet.2026.111941_bib11","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1038\/s41573-021-00283-5","article-title":"mRNA vaccines for infectious diseases: principles, delivery and clinical translation","volume":"20","author":"Chaudhary","year":"2021","journal-title":"Nat. Rev. Drug. Discov."},{"key":"10.1016\/j.toxlet.2026.111941_bib12","doi-asserted-by":"crossref","DOI":"10.1016\/j.vaccine.2025.128136","article-title":"Herpes zoster mRNA vaccine elicits superior immune responses over licensed vaccines with a favorable safety profile in animal models","volume":"72","author":"Chen","year":"2026","journal-title":"Vaccine"},{"issue":"17","key":"10.1016\/j.toxlet.2026.111941_bib13","doi-asserted-by":"crossref","first-page":"8964","DOI":"10.7150\/thno.119545","article-title":"ApoE deficiency protects from mRNA vaccine-induced mitochondrial dysfunction at the injection site under metabolic stress","volume":"15","author":"Cho","year":"2025","journal-title":"Theranostics"},{"issue":"11","key":"10.1016\/j.toxlet.2026.111941_bib14","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/j.tibtech.2023.05.007","article-title":"Rise of the RNA machines\u2013self-amplification in mRNA vaccine design","volume":"41","author":"Comes","year":"2023","journal-title":"Trends Biotechnol."},{"key":"10.1016\/j.toxlet.2026.111941_bib15","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.omtm.2019.01.010","article-title":"EU regulatory pathways for ATMPs: standard, accelerated and adaptive pathways to marketing authorisation","volume":"13","author":"Detela","year":"2019","journal-title":"Mol. Ther. Methods Clin. Dev."},{"issue":"2","key":"10.1016\/j.toxlet.2026.111941_bib16","doi-asserted-by":"crossref","DOI":"10.33992\/meditory.v13i2.4781","article-title":"Pseudouridine and N1-Methylpseudouridine in mRNA vaccines modulate retinoic acid inducible gene I (RIG-I) and toll-like receptors (TLR) activation","volume":"13","author":"Dewi","year":"2025","journal-title":"Meditory J. Med. Lab."},{"key":"10.1016\/j.toxlet.2026.111941_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.yrtph.2024.105769","article-title":"Global regulatory considerations and practices for tumorigenicity evaluation of cell-based therapy","volume":"156","author":"Dou","year":"2025","journal-title":"Regul. Toxicol. Pharmacol."},{"issue":"3","key":"10.1016\/j.toxlet.2026.111941_bib18","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2023.112189","article-title":"SARS-CoV-2 Spike protein induces TLR4-mediated long-term cognitive dysfunction recapitulating post-COVID-19 syndrome in mice","volume":"42","author":"Fontes-Dantas","year":"2023","journal-title":"Cell. Rep."},{"issue":"5-6","key":"10.1016\/j.toxlet.2026.111941_bib19","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.cca.2009.12.009","article-title":"Cardiac troponin may be released by ischemia alone, without necrosis","volume":"411","author":"Hickman","year":"2010","journal-title":"Clin. Chim. Acta"},{"issue":"12","key":"10.1016\/j.toxlet.2026.111941_bib20","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1038\/s41578-021-00358-0","article-title":"Lipid nanoparticles for mRNA delivery","volume":"6","author":"Hou","year":"2021","journal-title":"Nat. Rev. Mater."},{"issue":"4","key":"10.1016\/j.toxlet.2026.111941_bib21","doi-asserted-by":"crossref","DOI":"10.1016\/j.omtn.2025.102721","article-title":"mRNA therapeutics: Transforming medicine through innovation in design, delivery, and disease treatment","volume":"36","author":"Ige","year":"2025","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"10.1016\/j.toxlet.2026.111941_bib22","doi-asserted-by":"crossref","first-page":"921","DOI":"10.3389\/fphar.2019.00921","article-title":"Regulatory framework for advanced therapy medicinal products in Europe and United States","volume":"10","author":"Iglesias-L\u00f3pez","year":"2019","journal-title":"Front. Pharmacol."},{"issue":"26","key":"10.1016\/j.toxlet.2026.111941_bib23","doi-asserted-by":"crossref","first-page":"6867","DOI":"10.1016\/j.biomaterials.2010.05.027","article-title":"The systemic toxicity of positively charged lipid nanoparticles and the role of Toll-like receptor 4 in immune activation","volume":"31","author":"Kedmi","year":"2010","journal-title":"Biomaterials"},{"issue":"36","key":"10.1016\/j.toxlet.2026.111941_bib24","doi-asserted-by":"crossref","first-page":"24842","DOI":"10.1021\/acsnano.4c05088","article-title":"Lipid nanoparticles elicit reactogenicity and sickness behavior in mice via toll-like receptor 4 and myeloid differentiation protein 88 axis","volume":"18","author":"Korzun","year":"2024","journal-title":"ACS Nano"},{"key":"10.1016\/j.toxlet.2026.111941_bib25","doi-asserted-by":"crossref","DOI":"10.1016\/j.omtn.2026.102954","article-title":"Comparative analysis of expression dynamics, immunogenicity, and safety profiles between linear and circular RNA vaccine platforms","volume":"37","author":"Lee","year":"2026","journal-title":"Mol. Ther. - Nucleic Acids"},{"issue":"1","key":"10.1016\/j.toxlet.2026.111941_bib26","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41541-024-00825-z","article-title":"Assessing the impact of mRNA vaccination in chronic inflammatory murine model","volume":"9","author":"Lee","year":"2024","journal-title":"npj Vaccin."},{"issue":"2","key":"10.1016\/j.toxlet.2026.111941_bib27","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1038\/s41551-023-01082-6","article-title":"Enhancing the immunogenicity of lipid-nanoparticle mRNA vaccines by adjuvanting the ionizable lipid and the mRNA","volume":"9","author":"Li","year":"2025","journal-title":"Nat. Biomed. Eng."},{"key":"10.1016\/j.toxlet.2026.111941_bib28","doi-asserted-by":"crossref","DOI":"10.1016\/j.canlet.2024.217111","article-title":"Intratumoral injection of mRNA encoding survivin in combination with STAT3 inhibitor stattic enhances antitumor effects","volume":"598","author":"Li","year":"2024","journal-title":"Cancer Lett."},{"issue":"1","key":"10.1016\/j.toxlet.2026.111941_bib29","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1038\/s41541-024-00925-w","article-title":"Safety and efficacy assessment of an mRNA rabies vaccine in dogs, rodents, and cynomolgus macaques","volume":"9","author":"Li","year":"2024","journal-title":"npj Vaccin."},{"issue":"12","key":"10.1016\/j.toxlet.2026.111941_bib30","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2025373118","article-title":"Functional and genetic analysis of viral receptor ACE2 orthologs reveals a broad potential host range of SARS-CoV-2","volume":"118","author":"Liu","year":"2021","journal-title":"Proc. Natl. Acad. Sci."},{"issue":"18","key":"10.1016\/j.toxlet.2026.111941_bib31","doi-asserted-by":"crossref","first-page":"11329","DOI":"10.1039\/D5NR00433K","article-title":"PEGylated lipid screening, composition optimization, and structure\u2013activity relationship determination for lipid nanoparticle-mediated mRNA delivery","volume":"17","author":"Liu","year":"2025","journal-title":"Nanoscale"},{"key":"10.1016\/j.toxlet.2026.111941_bib32","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.jconrel.2022.03.021","article-title":"Intratumoral delivery of IL-12 and IL-27 mRNA using lipid nanoparticles for cancer immunotherapy","volume":"345","author":"Liu","year":"2022","journal-title":"J. Control. Release"},{"issue":"1","key":"10.1016\/j.toxlet.2026.111941_bib33","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s12929-024-01080-z","article-title":"Current landscape of mRNA technologies and delivery systems for new modality therapeutics","volume":"31","author":"Lu","year":"2024","journal-title":"J. Biomed. Sci."},{"issue":"4","key":"10.1016\/j.toxlet.2026.111941_bib34","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.ymthe.2019.01.020","article-title":"mRNA as a transformative technology for vaccine development to control infectious diseases","volume":"27","author":"Maruggi","year":"2019","journal-title":"Mol. Ther."},{"issue":"S2","key":"10.1016\/j.toxlet.2026.111941_bib35","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1089\/gen.42.S2.01","article-title":"Developing Tomorrow's mRNA-Based Therapies: New technologies\u2014such as circular mRNA, self-amplifying mRNA, programmable mRNA, and Cas13-encoding mRNA\u2014point to more powerful mRNA-based treatments","volume":"42","author":"May","year":"2022","journal-title":"Genet. Eng. Biotechnol. N."},{"issue":"9","key":"10.1016\/j.toxlet.2026.111941_bib36","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1038\/sj.cgt.7701072","article-title":"mRNA-based cancer vaccine: prevention of B16 melanoma progression and metastasis by systemic injection of MART1 mRNA histidylated lipopolyplexes","volume":"14","author":"Mockey","year":"2007","journal-title":"Cancer gene Ther."},{"issue":"21-22","key":"10.1016\/j.toxlet.2026.111941_bib37","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1089\/hum.2022.090","article-title":"Regulatory consideration for the nonclinical safety assessment of gene therapies","volume":"33","author":"Moffit","year":"2022","journal-title":"Human. Gene Ther."},{"issue":"1","key":"10.1016\/j.toxlet.2026.111941_bib38","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1097\/j.pain.0000000000002097","article-title":"SARS-CoV-2 spike protein co-opts VEGF-A\/neuropilin-1 receptor signaling to induce analgesia","volume":"162","author":"Moutal","year":"2021","journal-title":"Pain"},{"issue":"19","key":"10.1016\/j.toxlet.2026.111941_bib39","doi-asserted-by":"crossref","first-page":"14820","DOI":"10.3390\/ijms241914820","article-title":"The dual role of the innate immune system in the effectiveness of mRNA therapeutics","volume":"24","author":"Muslimov","year":"2023","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"10.1016\/j.toxlet.2026.111941_bib40","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1038\/s41392-023-01561-x","article-title":"Circular RNA vaccine in disease prevention and treatment","volume":"8","author":"Niu","year":"2023","journal-title":"Signal. Transduct. Target. Ther."},{"issue":"30","key":"10.1016\/j.toxlet.2026.111941_bib41","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1080\/17435889.2024.2419815","article-title":"Design and development of mRNA and self-amplifying mRNA vaccine nanoformulations","volume":"19","author":"Omidi","year":"2024","journal-title":"Nanomedicine"},{"issue":"3","key":"10.1016\/j.toxlet.2026.111941_bib42","doi-asserted-by":"crossref","DOI":"10.1128\/Spectrum.00735-21","article-title":"SARS-CoV-2 spike protein destabilizes microvascular homeostasis","volume":"9","author":"Panigrahi","year":"2021","journal-title":"Microbiol. Spectr."},{"issue":"1","key":"10.1016\/j.toxlet.2026.111941_bib43","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/s41541-023-00684-0","article-title":"Analyzing immune responses to varied mRNA and protein vaccine sequences","volume":"8","author":"Park","year":"2023","journal-title":"npj Vaccin."},{"issue":"4","key":"10.1016\/j.toxlet.2026.111941_bib44","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1080\/14779072.2022.2066522","article-title":"Myocarditis following COVID-19 vaccination: incidence, mechanisms, and clinical considerations","volume":"20","author":"Power","year":"2022","journal-title":"Expert. Rev. Cardiovasc. Ther."},{"issue":"1","key":"10.1016\/j.toxlet.2026.111941_bib45","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1038\/s41541-023-00733-8","article-title":"mRNA-LNP vaccination-based immunotherapy augments CD8+ T cell responses against HPV-positive oropharyngeal cancer","volume":"8","author":"Qiu","year":"2023","journal-title":"npj Vaccin."},{"key":"10.1016\/j.toxlet.2026.111941_bib46","series-title":"International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use","article-title":"Preclinical Safety Evaluation of Biotechnology-Derived Pharmaceuticals","author":"R1 IHTGS","year":"2011"},{"issue":"7","key":"10.1016\/j.toxlet.2026.111941_bib47","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1016\/S0002-9149(99)00020-X","article-title":"Cardiac troponin T and I, electrocardiographic wall motion analyses, and ejection fractions in athletes participating in the Hawaii Ironman Triathlon","volume":"83","author":"Rifai","year":"1999","journal-title":"Am. J. Cardiol."},{"key":"10.1016\/j.toxlet.2026.111941_bib48","series-title":"Guidance for Industry: Preclinical Assessment of Investigational Cellular and Gene Therapy Products","author":"Services USDoHaH","year":"2025"},{"key":"10.1016\/j.toxlet.2026.111941_bib49","doi-asserted-by":"crossref","DOI":"10.1016\/j.isci.2025.113498","article-title":"Comparison of immunogenicity and protection efficacy of self-amplifying and circular mRNA vaccines against SARS-CoV-2","author":"Singh","year":"2025","journal-title":"Iscience"},{"issue":"5","key":"10.1016\/j.toxlet.2026.111941_bib50","doi-asserted-by":"crossref","first-page":"473","DOI":"10.3390\/vaccines13050473","article-title":"Considerations for mRNA product development, regulation and deployment across the lifecycle","volume":"13","author":"Skerritt","year":"2025","journal-title":"Vaccines"},{"issue":"5","key":"10.1016\/j.toxlet.2026.111941_bib51","doi-asserted-by":"crossref","first-page":"528","DOI":"10.3390\/vaccines12050528","article-title":"The platform technology approach to mRNA product development and regulation","volume":"12","author":"Skerritt","year":"2024","journal-title":"Vaccines"},{"key":"10.1016\/j.toxlet.2026.111941_bib52","series-title":"Nonclinical Safety Assessment of Oligonucleotide-Based Therapeutics Guidance for Industry","author":"USDoHaH","year":"2024"},{"issue":"11","key":"10.1016\/j.toxlet.2026.111941_bib53","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1016\/j.immuni.2022.10.014","article-title":"Innate immune mechanisms of mRNA vaccines","volume":"55","author":"Verbeke","year":"2022","journal-title":"Immunity"},{"issue":"1","key":"10.1016\/j.toxlet.2026.111941_bib54","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1038\/s41467-018-05096-6","article-title":"Engineering circular RNA for potent and stable translation in eukaryotic cells","volume":"9","author":"Wesselhoeft","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.toxlet.2026.111941_bib55","series-title":"WHO Guidelines on Non Clinical Evaluation of Vaccines","author":"WHO","year":"2005"},{"key":"10.1016\/j.toxlet.2026.111941_bib56","series-title":"Evaluation of the Quality, Safety and Efficacy of Messenger RNA Vaccines for the Prevention of Infectious Diseases: Regulatory Considerations","author":"WHO","year":"2021"},{"issue":"7","key":"10.1016\/j.toxlet.2026.111941_bib57","article-title":"Novel less toxic, lymphoid tissue-targeted lipid nanoparticles containing a vitamin B5-derived ionizable lipid for mRNA vaccine delivery","volume":"14","author":"Yoo","year":"2025","journal-title":"Adv. Healthc. Mater."},{"issue":"1","key":"10.1016\/j.toxlet.2026.111941_bib58","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/s41541-025-01124-x","article-title":"Ionizable lipid nanoparticles of mRNA vaccines elicit NF-\u03baB and IRF responses through toll-like receptor 4","volume":"10","author":"Zelkoski","year":"2025","journal-title":"npj Vaccin."},{"key":"10.1016\/j.toxlet.2026.111941_bib59","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.jconrel.2025.01.071","article-title":"Role of PEGylated lipid in lipid nanoparticle formulation for in vitro and in vivo delivery of mRNA vaccines","volume":"380","author":"Zhang","year":"2025","journal-title":"J. Control. Release"},{"issue":"7","key":"10.1016\/j.toxlet.2026.111941_bib60","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1038\/s41422-021-00495-9","article-title":"SARS-CoV-2 spike protein interacts with and activates TLR41","volume":"31","author":"Zhao","year":"2021","journal-title":"Cell. Res."}],"container-title":["Toxicology Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378427426001244?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378427426001244?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T19:49:10Z","timestamp":1789328950000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0378427426001244"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":60,"alternative-id":["S0378427426001244"],"URL":"https:\/\/doi.org\/10.1016\/j.toxlet.2026.111941","relation":{},"ISSN":["0378-4274"],"issn-type":[{"value":"0378-4274","type":"print"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Nonclinical safety evaluation strategies for mRNA\/LNPs platform agents: Evidence from comprehensive animal toxicity studies","name":"articletitle","label":"Article Title"},{"value":"Toxicology Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.toxlet.2026.111941","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"111941"}}