{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T12:25:29Z","timestamp":1794313529736,"version":"4.9.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":40,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515012496"],"award-info":[{"award-number":["2024A1515012496"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Messenger RNA (mRNA)-based therapeutics hold great potential for effectively treating various diseases. However, the targeting of mRNA delivered by systemically administered lipid nanoparticles (LNP) is currently limited to the liver. Safe and efficient systemic delivery of mRNA to specific organs and cells remains a major challenge, and it is still unclear whether the positional isomerism of individual compounds within LNP affects their activity. Here, we synthesize a library of meta\/ortho\/para-ionizable lipidoids and prepare three-component lipid nanoparticles (tLNP) without PEG-lipids. Our findings show that tLNP containing meta-ionizable lipidoids (meta-tLNP) exhibits higher mRNA delivery efficiency than those containing ortho-\/para-ionizable lipidoids (ortho-\/para-tLNP). Additionally, we report a strategy termed Sequential Selective Organ-to-Cell Targeting (SSOCT), which enables the systemic administration of meta\/ortho\/para-tLNP to first achieve selective mRNA expression in the spleen, followed by targeted mRNA expression in dendritic cells within the spleen. Notably, we demonstrate that delivering the mRNA vaccine (mXO10 tLNP@mIDH1) using meta-tLNP effectively treats glioma in mice, particularly when combined with Anti-PD-1 therapy. This combination further enhances therapeutic efficacy, even completely eradicating glioma, reducing hepatotoxicity, and minimizing PEG-lipid-induced allergic reactions. This study establishes that mRNA therapy, developed by selectively targeting splenic dendritic cells via SSOCT, represents a promising therapeutic intervention for glioma.<\/jats:p>","DOI":"10.1038\/s41467-025-67331-1","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T15:23:20Z","timestamp":1765466600000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["mRNA vaccine developed for sequential selective organ-to-cell targeting of glioma"],"prefix":"10.1038","volume":"17","author":[{"given":"Lin","family":"Shi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuyao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuoyu","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8897-4891","authenticated-orcid":false,"given":"Wenbin","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3452-094X","authenticated-orcid":false,"given":"Guanjun","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,11]]},"reference":[{"key":"67331_CR1","doi-asserted-by":"publisher","first-page":"2273","DOI":"10.1038\/s41591-022-02061-1","volume":"28","author":"X Huang","year":"2022","unstructured":"Huang, X. et al. The landscape of mRNA nanomedicine. Nat. Med. 28, 2273\u20132287 (2022).","journal-title":"Nat. Med."},{"key":"67331_CR2","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1038\/s41587-022-01294-2","volume":"40","author":"AJ Barbier","year":"2022","unstructured":"Barbier, A. J., Jiang, A. Y., Zhang, P., Wooster, R. & Anderson, D. G. The clinical progress of mRNA vaccines and immunotherapies. Nat. Biotechnol. 40, 840\u2013854 (2022).","journal-title":"Nat. Biotechnol."},{"key":"67331_CR3","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s12929-022-00852-9","volume":"29","author":"M Kumari","year":"2022","unstructured":"Kumari, M. et al. A critical overview of current progress for COVID-19: development of vaccines, antiviral drugs, and therapeutic antibodies. J. Biomed. Sci. 29, 68 (2022).","journal-title":"J. Biomed. Sci."},{"key":"67331_CR4","doi-asserted-by":"publisher","first-page":"1316","DOI":"10.1016\/j.ymthe.2017.03.035","volume":"25","author":"K Bahl","year":"2017","unstructured":"Bahl, K. et al. Preclinical and clinical demonstration of immunogenicity by mRNA vaccines against H10N8 and H7N9 influenza viruses. Mol. Ther. 25, 1316\u20131327 (2017).","journal-title":"Mol. Ther."},{"key":"67331_CR5","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1016\/j.ymthe.2020.04.018","volume":"28","author":"AW Freyn","year":"2020","unstructured":"Freyn, A. W. et al. A multi-targeting, nucleoside-modified mRNA influenza virus vaccine provides broad protection in mice. Mol. Ther. 28, 1569\u20131584 (2020).","journal-title":"Mol. Ther."},{"key":"67331_CR6","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/S2213-2600(21)00557-9","volume":"10","author":"R Izikson","year":"2022","unstructured":"Izikson, R. et al. Safety and immunogenicity of a high-dose quadrivalent influenza vaccine administered concomitantly with a third dose of the mRNA-1273 SARS-CoV-2 vaccine in adults aged >\/=65 years: a phase 2, randomised, open-label study. Lancet. Respir. Med. 10, 392\u2013402 (2022).","journal-title":"Lancet. Respir. Med."},{"key":"67331_CR7","doi-asserted-by":"publisher","first-page":"7409","DOI":"10.1016\/j.vaccine.2020.09.079","volume":"38","author":"PC LaTourette","year":"2020","unstructured":"LaTourette, P. C. et al. Protection against herpes simplex virus type 2 infection in a neonatal murine model using a trivalent nucleoside-modified mRNA in lipid nanoparticle vaccine. Vaccine 38, 7409\u20137413 (2020).","journal-title":"Vaccine"},{"key":"67331_CR8","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1038\/s41591-023-02786-7","volume":"30","author":"K Wang","year":"2024","unstructured":"Wang, K. et al. Adjuvant sintilimab in resected high-risk hepatocellular carcinoma: a randomized, controlled, phase 2 trial. Nat. Med. 30, 708\u2013715 (2024).","journal-title":"Nat. Med."},{"key":"67331_CR9","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1038\/s41551-023-01030-4","volume":"7","author":"LH Rhym","year":"2023","unstructured":"Rhym, L. H., Manan, R. S., Koller, A., Stephanie, G. & Anderson, D. G. Peptide-encoding mRNA barcodes for the high-throughput in vivo screening of libraries of lipid nanoparticles for mRNA delivery. Nat. Biomed. Eng. 7, 901\u2013910 (2023).","journal-title":"Nat. Biomed. Eng."},{"key":"67331_CR10","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202201095","volume":"34","author":"R Pattipeiluhu","year":"2022","unstructured":"Pattipeiluhu, R. et al. Anionic lipid nanoparticles preferentially deliver mRNA to the hepatic reticuloendothelial system. Adv. Mater. 34, e2201095 (2022).","journal-title":"Adv. Mater."},{"key":"67331_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16248-y","volume":"11","author":"L Miao","year":"2020","unstructured":"Miao, L. et al. Synergistic lipid compositions for albumin receptor mediated delivery of mRNA to the liver. Nat. Commun. 11, 2424 (2020).","journal-title":"Nat. Commun."},{"key":"67331_CR12","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1016\/S0140-6736(23)02444-3","volume":"403","author":"H Parhiz","year":"2024","unstructured":"Parhiz, H., Atochina-Vasserman, E. N. & Weissman, D. mRNA-based therapeutics: looking beyond COVID-19 vaccines. Lancet 403, 1192\u20131204 (2024).","journal-title":"Lancet"},{"key":"67331_CR13","doi-asserted-by":"publisher","first-page":"16982","DOI":"10.1021\/acsnano.1c04996","volume":"15","author":"R Tenchov","year":"2021","unstructured":"Tenchov, R., Bird, R., Curtze, A. E. & Zhou, Q. Lipid nanoparticles horizontal line from liposomes to mRNA vaccine delivery, a landscape of research diversity and advancement. ACS Nano 15, 16982\u201317015 (2021).","journal-title":"ACS Nano"},{"key":"67331_CR14","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1038\/s41565-020-0669-6","volume":"15","author":"Q Cheng","year":"2020","unstructured":"Cheng, Q. et al. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR\u2013Cas gene editing. Nat. Nanotechnol. 15, 313\u2013320 (2020).","journal-title":"Nat. Nanotechnol."},{"key":"67331_CR15","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1126\/science.ade6967","volume":"381","author":"L Breda","year":"2023","unstructured":"Breda, L. et al. In vivo hematopoietic stem cell modification by mRNA delivery. Science 381, 436\u2013443 (2023).","journal-title":"Science"},{"key":"67331_CR16","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1038\/s41565-024-01680-8","volume":"19","author":"X Lian","year":"2024","unstructured":"Lian, X. et al. Bone-marrow-homing lipid nanoparticles for genome editing in diseased and malignant haematopoietic stem cells. Nat. Nanotechnol. 19, 1409\u20131417 (2024).","journal-title":"Nat. Nanotechnol."},{"key":"67331_CR17","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202301929","volume":"10","author":"GS Naidu","year":"2023","unstructured":"Naidu, G. S. et al. A combinatorial library of lipid nanoparticles for cell type-specific mRNA delivery. Adv. Sci. 10, e2301929 (2023).","journal-title":"Adv. Sci."},{"key":"67331_CR18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2116271119","volume":"119","author":"M Qiu","year":"2022","unstructured":"Qiu, M. et al. Lung-selective mRNA delivery of synthetic lipid nanoparticles for the treatment of pulmonary lymphangioleiomyomatosis. Proc. Natl. Acad. Sci. USA 119, e2116271119 (2022).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"67331_CR19","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202303261","volume":"35","author":"Y Zong","year":"2023","unstructured":"Zong, Y., Lin, Y., Wei, T. & Cheng, Q. Lipid nanoparticle (LNP) enables mRNA delivery for cancer therapy. Adv. Mater. 35, e2303261 (2023).","journal-title":"Adv. Mater."},{"key":"67331_CR20","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1038\/s41573-024-00977-6","volume":"23","author":"PR Cullis","year":"2024","unstructured":"Cullis, P. R. & Felgner, P. L. The 60-year evolution of lipid nanoparticles for nucleic acid delivery. Nat. Rev. Drug. Discov. 23, 709\u2013722 (2024).","journal-title":"Nat. Rev. Drug. Discov."},{"key":"67331_CR21","doi-asserted-by":"publisher","first-page":"114416","DOI":"10.1016\/j.addr.2022.114416","volume":"188","author":"C Hald Albertsen","year":"2022","unstructured":"Hald Albertsen, C. et al. The role of lipid components in lipid nanoparticles for vaccines and gene therapy. Adv. Drug. Deliv. Rev. 188, 114416 (2022).","journal-title":"Adv. Drug. Deliv. Rev."},{"key":"67331_CR22","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1038\/s41557-023-01138-9","volume":"15","author":"MZC Hatit","year":"2023","unstructured":"Hatit, M. Z. C. et al. Nanoparticle stereochemistry-dependent endocytic processing improves in vivo mRNA delivery. Nat. Chem. 15, 508\u2013515 (2023).","journal-title":"Nat. Chem."},{"key":"67331_CR23","doi-asserted-by":"publisher","first-page":"2294","DOI":"10.1021\/jacs.2c10670","volume":"145","author":"G Tilstra","year":"2023","unstructured":"Tilstra, G. et al. Iterative design of ionizable lipids for intramuscular mRNA delivery. J. Am. Chem. Soc. 145, 2294\u20132304 (2023).","journal-title":"J. Am. Chem. Soc."},{"key":"67331_CR24","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.jconrel.2024.10.028","volume":"376","author":"S Wu","year":"2024","unstructured":"Wu, S. et al. Paracyclophane-based ionizable lipids for efficient mRNA delivery in vivo. J. Control. Release 376, 395\u2013401 (2024).","journal-title":"J. Control. Release"},{"key":"67331_CR25","doi-asserted-by":"publisher","first-page":"101705","DOI":"10.1016\/j.cocis.2023.101705","volume":"66","author":"M C\u00e1rdenas","year":"2023","unstructured":"C\u00e1rdenas, M., Campbell, R. A., Yanez Arteta, M., Lawrence, M. J. & Sebastiani, F. Review of structural design guiding the development of lipid nanoparticles for nucleic acid delivery. Curr. Opin. Colloid. Interface. Sci. 66, 101705 (2023).","journal-title":"Curr. Opin. Colloid. Interface. Sci."},{"key":"67331_CR26","doi-asserted-by":"publisher","first-page":"6527","DOI":"10.1039\/D3TB00649B","volume":"11","author":"Y Xu","year":"2023","unstructured":"Xu, Y., Golubovic, A., Xu, S., Pan, A. & Li, B. Rational design and combinatorial chemistry of ionizable lipids for RNA delivery. J. Mater. Chem. B 11, 6527\u20136539 (2023).","journal-title":"J. Mater. Chem. B"},{"key":"67331_CR27","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202310401","volume":"62","author":"Z He","year":"2023","unstructured":"He, Z. et al. A multidimensional approach to modulating ionizable lipids for high-performing and organ-selective mRNA delivery. Angew. Chem. Int. Ed. Engl 62, e202310401 (2023).","journal-title":"Angew. Chem. Int. Ed. Engl"},{"key":"67331_CR28","doi-asserted-by":"publisher","first-page":"12181","DOI":"10.1021\/acs.chemrev.1c00244","volume":"121","author":"Y Zhang","year":"2021","unstructured":"Zhang, Y., Sun, C., Wang, C., Jankovic, K. E. & Dong, Y. Lipids and lipid derivatives for RNA delivery. Chem. Rev. 121, 12181\u201312277 (2021).","journal-title":"Chem. Rev."},{"key":"67331_CR29","doi-asserted-by":"publisher","first-page":"114079","DOI":"10.1016\/j.addr.2021.114079","volume":"180","author":"D Shi","year":"2022","unstructured":"Shi, D. et al. To PEGylate or not to PEGylate: immunological properties of nanomedicine\u2019s most popular component, polyethylene glycol and its alternatives. Adv. Drug. Deliv. Rev. 180, 114079 (2022).","journal-title":"Adv. Drug. Deliv. Rev."},{"key":"67331_CR30","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1038\/s41587-022-01491-z","volume":"40","author":"E Rohner","year":"2022","unstructured":"Rohner, E., Yang, R., Foo, K. S., Goedel, A. & Chien, K. R. Unlocking the promise of mRNA therapeutics. Nat. Biotechnol. 40, 1586\u20131600 (2022).","journal-title":"Nat. Biotechnol."},{"key":"67331_CR31","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/nrclinonc.2017.171","volume":"15","author":"N Sanai","year":"2018","unstructured":"Sanai, N. & Berger, M. S. Surgical oncology for gliomas: the state of the art. Nat. Rev. Clin. Oncol. 15, 112\u2013125 (2018).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"67331_CR32","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.canlet.2020.02.002","volume":"476","author":"S Xu","year":"2020","unstructured":"Xu, S., Tang, L., Li, X., Fan, F. & Liu, Z. Immunotherapy for glioma: current management and future application. Cancer Lett. 476, 1\u201312 (2020).","journal-title":"Cancer Lett."},{"key":"67331_CR33","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/s41582-019-0220-2","volume":"15","author":"AM Molinaro","year":"2019","unstructured":"Molinaro, A. M., Taylor, J. W., Wiencke, J. K. & Wrensch, M. R. Genetic and molecular epidemiology of adult diffuse glioma. Nat. Rev. Neurol. 15, 405\u2013417 (2019).","journal-title":"Nat. Rev. Neurol."},{"key":"67331_CR34","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1038\/s41423-020-0488-6","volume":"17","author":"Y Zhang","year":"2020","unstructured":"Zhang, Y. & Zhang, Z. The history and advances in cancer immunotherapy: understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications. Cell. Mol. Immunol. 17, 807\u2013821 (2020).","journal-title":"Cell. Mol. Immunol."},{"key":"67331_CR35","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/s41573-018-0006-z","volume":"18","author":"RS Riley","year":"2019","unstructured":"Riley, R. S., June, C. H., Langer, R. & Mitchell, M. J. Delivery technologies for cancer immunotherapy. Nat. Rev. Drug. Discov. 18, 175\u2013196 (2019).","journal-title":"Nat. Rev. Drug. Discov."},{"key":"67331_CR36","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1038\/nri.2017.131","volume":"18","author":"Z Hu","year":"2018","unstructured":"Hu, Z., Ott, P. A. & Wu, C. J. Towards personalized, tumour-specific, therapeutic vaccines for cancer. Nat. Rev. Immunol. 18, 168\u2013182 (2018).","journal-title":"Nat. Rev. Immunol."},{"key":"67331_CR37","doi-asserted-by":"publisher","first-page":"911","DOI":"10.1038\/s43018-022-00418-6","volume":"3","author":"MJ Lin","year":"2022","unstructured":"Lin, M. J. et al. Cancer vaccines: the next immunotherapy frontier. Nat. Cancer 3, 911\u2013926 (2022).","journal-title":"Nat. Cancer"},{"key":"67331_CR38","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s13045-022-01247-x","volume":"15","author":"J Liu","year":"2022","unstructured":"Liu, J. et al. Cancer vaccines as promising immuno-therapeutics: platforms and current progress. J. Hematol. Oncol. 15, 28 (2022).","journal-title":"J. Hematol. Oncol."},{"key":"67331_CR39","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1038\/s41392-022-00950-y","volume":"7","author":"E Fang","year":"2022","unstructured":"Fang, E. et al. Advances in COVID-19 mRNA vaccine development. Signal. Transduct. Target. Ther. 7, 94 (2022).","journal-title":"Signal. Transduct. Target. Ther."},{"key":"67331_CR40","doi-asserted-by":"publisher","first-page":"e450","DOI":"10.1016\/S1470-2045(22)00372-2","volume":"23","author":"CL Lorentzen","year":"2022","unstructured":"Lorentzen, C. L., Haanen, J. B., Met, O. & Svane, I. M. Clinical advances and ongoing trials on mRNA vaccines for cancer treatment. Lancet. Oncol. 23, e450\u2013e458 (2022).","journal-title":"Lancet. Oncol."},{"key":"67331_CR41","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-021-01335-5","volume":"20","author":"L Miao","year":"2021","unstructured":"Miao, L., Zhang, Y. & Huang, L. mRNA vaccine for cancer immunotherapy. Mol. Cancer 20, 41 (2021).","journal-title":"Mol. Cancer"},{"key":"67331_CR42","doi-asserted-by":"publisher","first-page":"115446","DOI":"10.1016\/j.addr.2024.115446","volume":"214","author":"K Mrksich","year":"2024","unstructured":"Mrksich, K., Padilla, M. S. & Mitchell, M. J. Breaking the final barrier: evolution of cationic and ionizable lipid structure in lipid nanoparticles to escape the endosome. Adv. Drug. Deliv. Rev. 214, 115446 (2024).","journal-title":"Adv. Drug. Deliv. Rev."},{"key":"67331_CR43","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1080\/17425247.2021.1873272","volume":"18","author":"M Hajimolaali","year":"2021","unstructured":"Hajimolaali, M. et al. Application of chloroquine as an endosomal escape enhancing agent: new frontiers for an old drug. Expert. Opin. Drug. Deliv. 18, 877\u2013889 (2021).","journal-title":"Expert. Opin. Drug. Deliv."},{"key":"67331_CR44","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1093\/annonc\/mdw013","volume":"27","author":"L Dang","year":"2016","unstructured":"Dang, L., Yen, K. & Attar, E. C. IDH mutations in cancer and progress toward development of targeted therapeutics. Ann. Oncol. 27, 599\u2013608 (2016).","journal-title":"Ann. Oncol."}],"updated-by":[{"DOI":"10.1038\/s41467-026-75443-5","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000}}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-67331-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-67331-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-67331-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T11:52:09Z","timestamp":1794311529000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-67331-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,11]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["67331"],"URL":"https:\/\/doi.org\/10.1038\/s41467-025-67331-1","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,11]]},"assertion":[{"value":"21 November 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2026","order":6,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":7,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41467-026-75443-5","URL":"https:\/\/doi.org\/10.1038\/s41467-026-75443-5","order":9,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"687"}}