{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T16:24:11Z","timestamp":1793550251690,"version":"4.5.0"},"reference-count":66,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"33","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,8,15]]},"abstract":"<jats:p>\n                    Efficient delivery of messenger RNA (mRNA) to the brain via systemic administration remains a challenge, primarily due to the blood-brain barrier. To address this challenge, we incorporated SR-57227, a ligand of serotonin [5-hydroxytryptamine type 3 (5-HT\n                    <jats:sub>3<\/jats:sub>\n                    )] receptor, into the design of ionizable lipids to develop lipid nanoparticles (LNPs) for systemic mRNA delivery to the brain. OS4T LNP was identified as an optimized formulation based on multiple assays. Following systemic administration, OS4T LNP achieved over a 50-fold increase in mRNA translation within brain tissues compared to US Food and Drug Administration\u2013approved Onpattro LNPs (DLin-MC3-DMA). In an orthotopic glioblastoma (GBM) mouse model, engineered interleukin-12 mRNA\u2013loaded OS4T LNPs significantly suppressed tumor growth and improved overall survival. This study demonstrates OS4T LNP as a promising platform for brain mRNA delivery and highlights its potential for treating GBM and other central nervous system disorders.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adw0730","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T17:59:04Z","timestamp":1755107944000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":78,"title":["Lipid nanoparticles for mRNA delivery in brain via systemic administration"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3776-7474","authenticated-orcid":true,"given":"Dinglingge","family":"Cao","sequence":"first","affiliation":[{"name":"Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7833-8704","authenticated-orcid":true,"given":"Xucheng","family":"Hou","sequence":"additional","affiliation":[{"name":"Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1630-9453","authenticated-orcid":true,"given":"Chang","family":"Wang","sequence":"additional","affiliation":[{"name":"Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5105-6709","authenticated-orcid":true,"given":"Zhengwei","family":"Liu","sequence":"additional","affiliation":[{"name":"Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7719-9896","authenticated-orcid":true,"given":"Meng","family":"Tian","sequence":"additional","affiliation":[{"name":"Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0621-9543","authenticated-orcid":true,"given":"Kaiyuan","family":"Guo","sequence":"additional","affiliation":[{"name":"Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana D.","family":"Kang","sequence":"additional","affiliation":[{"name":"Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA."},{"name":"Division of Pharmaceutics and Pharmacology, College of Pharmacy, The Ohio State University, Columbus, OH, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3652-1257","authenticated-orcid":true,"given":"Yichen","family":"Zhong","sequence":"additional","affiliation":[{"name":"Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6022-2487","authenticated-orcid":true,"given":"Yonger","family":"Xue","sequence":"additional","affiliation":[{"name":"Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1308-4269","authenticated-orcid":true,"given":"Changyue","family":"Yu","sequence":"additional","affiliation":[{"name":"Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binbin","family":"Deng","sequence":"additional","affiliation":[{"name":"Center for Electron Microscopy and Analysis, The Ohio State University, Columbus, OH, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5786-0659","authenticated-orcid":true,"given":"Yizhou","family":"Dong","sequence":"additional","affiliation":[{"name":"Icahn Genomics Institute, Precision Immunology Institute, Department of Immunology and Immunotherapy, Department of Oncological Sciences, Tisch Cancer Institute, Friedman Brain Institute, Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-022-01294-2"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/natrevmats.2017.56"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.1c00601"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41578-021-00358-0"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2023.115042"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202408744"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-020-0669-6"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-023-01563-4"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.ade6967"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abb4429"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00139-y"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-024-00829-7"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adi2245"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.138.4.877"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.3c03724"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00952-3"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-022-00965-4"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202208018"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abj4011"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c01824"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-024-02487-7"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(93)90282-M"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2018.11.174"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/nn4057269"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.9b00008"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.114044"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/339706a0"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2020.108155"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2019.119491"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202319700"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.4c05186"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2018.05.041"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-022-00938-7"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15623"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-023-01032-2"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0139652"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2019.08.004"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2022.1065193"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaw5680"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1001"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adh9879"},{"key":"e_1_3_2_43_2","first-page":"409","article-title":"Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies","volume":"3","author":"Atkins M. B.","year":"1997","unstructured":"M. B. Atkins, M. J. Robertson, M. Gordon, M. T. Lotze, M. DeCoste, J. S. DuBois, J. Ritz, A. B. Sandler, H. D. Edington, P. D. Garzone, J. W. Mier, C. M. Canning, L. Battiato, H. Tahara, M. L. Sherman, Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies. Clin. Cancer Res. 3, 409\u2013417 (1997).","journal-title":"Clin. Cancer Res."},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.952231"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-020-0549-2"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaw2614"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-023-01580-3"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-020-0095-6"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202400307"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-022-00888-0"},{"key":"e_1_3_2_51_2","first-page":"2541","article-title":"Effects of single-dose interleukin-12 exposure on interleukin-12\u2013associated toxicity and interferon-\u03b3 production","volume":"90","author":"Leonard J. P.","year":"1997","unstructured":"J. P. Leonard, M. L. Sherman, G. L. Fisher, L. J. Buchanan, G. Larsen, M. B. Atkins, J. A. Sosman, J. P. Dutcher, N. J. Vogelzang, J. L. Ryan, Effects of single-dose interleukin-12 exposure on interleukin-12\u2013associated toxicity and interferon-\u03b3 production. Blood 90, 2541\u20132548 (1997).","journal-title":"Blood"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17704-5"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2035389"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2034577"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-023-00811-9"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-023-00586-2"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-023-01453-9"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-024-01042-y"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202004025"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41563-023-01487-3"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2024.115446"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1089\/nat.2018.0734"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41578-024-00695-w"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202207486"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-022-00755-x"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2021.101019"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-022-01215-0"}],"container-title":["Science Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/sciadv.adw0730","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T17:59:06Z","timestamp":1755107946000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/sciadv.adw0730"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,15]]},"references-count":66,"journal-issue":{"issue":"33","published-print":{"date-parts":[[2025,8,15]]}},"alternative-id":["10.1126\/sciadv.adw0730"],"URL":"https:\/\/doi.org\/10.1126\/sciadv.adw0730","relation":{},"ISSN":["2375-2548"],"issn-type":[{"value":"2375-2548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,15]]},"assertion":[{"value":"2025-01-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadw0730"}}