{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T07:38:55Z","timestamp":1792481935276,"version":"4.5.0"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100003569","name":"Ministry of Food and Drug Safety","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003569","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korean government","award":["22213MFDS421"],"award-info":[{"award-number":["22213MFDS421"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Synthetic messenger RNA (mRNA) formulated in lipid nanoparticles (LNPs) is increasingly used for vaccines and therapeutics, yet the consequences of high-dose systemic exposure for bone marrow hematopoiesis remain poorly defined. We previously reported that intramuscular mRNA\/LNP administration transiently alters circulating reticulocytes and bone marrow erythroid cellularity in mice; here, we investigated the mechanistic basis and cross-species generalizability of this hematopoietic bias in murine and non-human primate models. Animals received intramuscular LNP-formulated mRNA encoding SARS-CoV-2 spike protein or firefly luciferase at deliberately supra-clinical, upper-bound doses, and type I interferon signaling was interrogated by interferon-\u03b1\/\u03b2 receptor blockade. Bone marrow was assessed by histopathology, bulk and single-cell RNA sequencing, and trajectory analysis. LNP-formulated mRNA induced reversible erythroid-lineage suppression with concomitant granulocytic expansion, irrespective of the encoded antigen. These effects were absent after naked mRNA and only modestly induced by LNP alone, indicating that formulation of synthetic mRNA within the LNP was required to elicit the full phenotype. Single-cell analysis showed biased hematopoietic stem and progenitor cell differentiation toward granulopoiesis with broad induction of interferon-stimulated genes, and the bias resolved within 2 wk. Interferon-\u03b1\/\u03b2 receptor blockade mitigated both changes, demonstrating type I interferon dependence. High-dose LNP-formulated synthetic mRNA can therefore drive reversible, type I interferon-dependent hematopoietic lineage bias in preclinical animal models.<\/jats:p>\n                  <jats:p>This study identifies type I interferon signaling as the driver of a reversible, dose-dependent shift in bone marrow hematopoiesis under upper-bound exposure to LNP-formulated synthetic mRNA, informing preclinical safety evaluation of the rapidly expanding class of nucleic acid-based therapeutics.<\/jats:p>","DOI":"10.1093\/toxsci\/kfag134","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T11:44:34Z","timestamp":1791459874000},"source":"Crossref","is-referenced-by-count":0,"title":["Lipid nanoparticle-formulated synthetic messenger RNA induces reversible hematopoietic bias via type I interferon responses under upper-bound inflammatory conditions in preclinical animal models"],"prefix":"10.1093","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4545-1211","authenticated-orcid":false,"given":"Jae-Hun","family":"Ahn","sequence":"first","affiliation":[{"name":"Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital , Seoul, 03080,","place":["Republic of Korea"]},{"name":"Transplantation Research Institute, Medical Research Center, Seoul National University , Seoul, 03080,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na-Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital , Seoul, 03080,","place":["Republic of Korea"]},{"name":"Department of Veterinary Pathology and Research Institute of Veterinary Science, College of Veterinary Medicine, Seoul National University , Seoul, 08826,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Jin","family":"Bae","sequence":"additional","affiliation":[{"name":"Graduate School of Translational Medicine, Seoul National University College of Medicine , Seoul, 03080,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jooil","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital , Seoul, 03080,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jina","family":"Kwak","sequence":"additional","affiliation":[{"name":"Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital , Seoul, 03080,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gahyun","family":"Roh","sequence":"additional","affiliation":[{"name":"Department of Medical and Biological Sciences, The Catholic University of Korea , Bucheon, Gyeonggi-do, 14662,","place":["Republic of Korea"]},{"name":"BK21 Plus, Department of Biotechnology, The Catholic University of Korea , Bucheon, Gyeonggi-do, 14662,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seo-Hyeon","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Medical and Biological Sciences, The Catholic University of Korea , Bucheon, Gyeonggi-do, 14662,","place":["Republic of Korea"]},{"name":"BK21 Plus, Department of Biotechnology, The Catholic University of Korea , Bucheon, Gyeonggi-do, 14662,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jisun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medical and Biological Sciences, The Catholic University of Korea , Bucheon, Gyeonggi-do, 14662,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae-Hwan","family":"Nam","sequence":"additional","affiliation":[{"name":"Department of Medical and Biological Sciences, The Catholic University of Korea , Bucheon, Gyeonggi-do, 14662,","place":["Republic of Korea"]},{"name":"BK21 Plus, Department of Biotechnology, The Catholic University of Korea , Bucheon, Gyeonggi-do, 14662,","place":["Republic of Korea"]},{"name":"National Institute of Health, Korea Disease Control and Prevention Agency , Cheongju-si, Chungcheongbuk-do, 28159,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medical and Biological Sciences, The Catholic University of Korea , Bucheon, Gyeonggi-do, 14662,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byeong-Cheol","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital , Seoul, 03080,","place":["Republic of Korea"]},{"name":"Graduate School of Translational Medicine, Seoul National University College of Medicine , Seoul, 03080,","place":["Republic of Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"2026102002512186200_kfag134-B1","doi-asserted-by":"publisher","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 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