{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:09:52Z","timestamp":1794002992328,"version":"4.8.0"},"reference-count":57,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-061250"],"award-info":[{"award-number":["INV-061250"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-061250"],"award-info":[{"award-number":["INV-061250"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-061250"],"award-info":[{"award-number":["INV-061250"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-061250"],"award-info":[{"award-number":["INV-061250"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-061250"],"award-info":[{"award-number":["INV-061250"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-061250"],"award-info":[{"award-number":["INV-061250"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-061250"],"award-info":[{"award-number":["INV-061250"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-061250"],"award-info":[{"award-number":["INV-061250"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-061250"],"award-info":[{"award-number":["INV-061250"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-061250"],"award-info":[{"award-number":["INV-061250"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-061250"],"award-info":[{"award-number":["INV-061250"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-061250"],"award-info":[{"award-number":["INV-061250"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-061250"],"award-info":[{"award-number":["INV-061250"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Biotechnol"],"DOI":"10.1038\/s41587-026-03331-w","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T09:02:46Z","timestamp":1790586166000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Accelerated discovery of thermostable mRNA\u2013lipid nanoparticle vaccines using data-efficient AI"],"prefix":"10.1038","author":[{"given":"Jinbi","family":"Tian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5331-4068","authenticated-orcid":false,"given":"Khanh T. M.","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett H.","family":"Pogostin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Sheridan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevinj","family":"Mursalova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy H.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaya","family":"Hamkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7301-7212","authenticated-orcid":false,"given":"Daniel","family":"Antov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alana L.","family":"Power","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zane S.","family":"Dash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9495-1613","authenticated-orcid":false,"given":"Dongsoo","family":"Yun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2895-0206","authenticated-orcid":false,"given":"Mina","family":"Konakovi\u0107 Lukovi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4255-0492","authenticated-orcid":false,"given":"Robert S.","family":"Langer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6096-0538","authenticated-orcid":false,"given":"Ana","family":"Jaklenec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"3331_CR1","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1056\/NEJMoa2035389","volume":"384","author":"LR Baden","year":"2021","unstructured":"Baden, L. R. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 384, 403\u2013416 (2021).","journal-title":"N. Engl. J. Med."},{"key":"3331_CR2","doi-asserted-by":"publisher","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","volume":"383","author":"FP Polack","year":"2020","unstructured":"Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N. Engl. J. Med. 383, 2603\u20132615 (2020).","journal-title":"N. Engl. J. Med."},{"key":"3331_CR3","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":"3331_CR4","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1016\/j.vaccine.2021.03.038","volume":"39","author":"SS Rosa","year":"2021","unstructured":"Rosa, S. S., Prazeres, D. M. F., Azevedo, A. M. & Marques, M. P. C. mRNA vaccines manufacturing: challenges and bottlenecks. Vaccine 39, 2190\u20132200 (2021).","journal-title":"Vaccine"},{"key":"3331_CR5","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1016\/j.xphs.2022.11.001","volume":"112","author":"E Oude Blenke","year":"2023","unstructured":"Oude Blenke, E. et al. The storage and in-use stability of mRNA vaccines and therapeutics: not a cold case. J. Pharm. Sci. 112, 386\u2013403 (2023).","journal-title":"J. Pharm. Sci."},{"key":"3331_CR6","unstructured":"Moderna COVID-19 Vaccine Summary https:\/\/www.cdc.gov\/vaccines\/php\/info-by-product\/moderna-covid-19-summary.html (Centers for Disease Control and Prevention, 2024)."},{"key":"3331_CR7","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1016\/j.xphs.2020.12.006","volume":"110","author":"DJA Crommelin","year":"2021","unstructured":"Crommelin, D. J. A., Anchordoquy, T. J., Volkin, D. B., Jiskoot, W. & Mastrobattista, E. Addressing the cold reality of mRNA vaccine stability. J. Pharm. Sci. 110, 997\u20131001 (2021).","journal-title":"J. Pharm. Sci."},{"key":"3331_CR8","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":"3331_CR9","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1007\/s00281-023-00998-0","volume":"45","author":"M Ferranna","year":"2024","unstructured":"Ferranna, M. Causes and costs of global COVID-19 vaccine inequity. Semin. Immunopathol. 45, 469\u2013480 (2024).","journal-title":"Semin. Immunopathol."},{"key":"3331_CR10","doi-asserted-by":"publisher","first-page":"120586","DOI":"10.1016\/j.ijpharm.2021.120586","volume":"601","author":"L Schoenmaker","year":"2021","unstructured":"Schoenmaker, L. et al. mRNA-lipid nanoparticle COVID-19 vaccines: structure and stability. Int. J. Pharm. 601, 120586 (2021).","journal-title":"Int. J. Pharm."},{"key":"3331_CR11","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1208\/s12249-022-02282-0","volume":"23","author":"J Musakhanian","year":"2022","unstructured":"Musakhanian, J., Rodier, J.-D. & Dave, M. Oxidative stability in lipid formulations: a review of the mechanisms, drivers, and inhibitors of oxidation. AAPS PharmSciTech 23, 151 (2022).","journal-title":"AAPS PharmSciTech"},{"key":"3331_CR12","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26926-0","volume":"12","author":"M Packer","year":"2021","unstructured":"Packer, M., Gyawali, D., Yerabolu, R., Schariter, J. & White, P. A novel mechanism for the loss of mRNA activity in lipid nanoparticle delivery systems. Nat. Commun. 12, 6777 (2021).","journal-title":"Nat. Commun."},{"key":"3331_CR13","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.jconrel.2022.11.022","volume":"353","author":"B Kim","year":"2023","unstructured":"Kim, B. et al. Optimization of storage conditions for lipid nanoparticle-formulated self-replicating RNA vaccines. J. Control. Release 353, 241\u2013253 (2023).","journal-title":"J. Control. Release"},{"key":"3331_CR14","doi-asserted-by":"publisher","first-page":"1941","DOI":"10.1016\/j.ymthe.2022.02.001","volume":"30","author":"H Muramatsu","year":"2022","unstructured":"Muramatsu, H. et al. Lyophilization provides long-term stability for a lipid nanoparticle-formulated, nucleoside-modified mRNA vaccine. Mol. Ther. 30, 1941\u20131951 (2022).","journal-title":"Mol. Ther."},{"key":"3331_CR15","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s41421-022-00517-9","volume":"9","author":"L Ai","year":"2023","unstructured":"Ai, L. et al. Lyophilized mRNA-lipid nanoparticle vaccines with long-term stability and high antigenicity against SARS-CoV-2. Cell Discov. 9, 9 (2023).","journal-title":"Cell Discov."},{"key":"3331_CR16","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1097\/AJP.0b013e31816778f9","volume":"24","author":"HS Gill","year":"2008","unstructured":"Gill, H. S., Denson, D. D., Burris, B. A. & Prausnitz, M. R. Effect of microneedle design on pain in human volunteers. Clin. J. Pain 24, 585\u2013594 (2008).","journal-title":"Clin. J. Pain"},{"key":"3331_CR17","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1007\/s13346-016-0282-2","volume":"7","author":"MJ Mistilis","year":"2017","unstructured":"Mistilis, M. J. et al. Long-term stability of influenza vaccine in a dissolving microneedle patch. Drug Deliv. Transl. Res. 7, 195\u2013205 (2017).","journal-title":"Drug Deliv. Transl. Res."},{"key":"3331_CR18","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1038\/s41587-023-01774-z","volume":"42","author":"A vander Straeten","year":"2024","unstructured":"vander Straeten, A. et al. A microneedle vaccine printer for thermostable COVID-19 mRNA vaccines. Nat. Biotechnol. 42, 510\u2013517 (2024).","journal-title":"Nat. Biotechnol."},{"key":"3331_CR19","doi-asserted-by":"publisher","first-page":"eabj1476","DOI":"10.1126\/sciadv.abj1476","volume":"7","author":"MT Mabrouk","year":"2021","unstructured":"Mabrouk, M. T. et al. Lyophilized, thermostable Spike or RBD immunogenic liposomes induce protective immunity against SARS-CoV-2 in mice. Sci. Adv. 7, eabj1476 (2021).","journal-title":"Sci. Adv."},{"key":"3331_CR20","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/j.jconrel.2024.07.052","volume":"373","author":"Y Fan","year":"2024","unstructured":"Fan, Y. et al. Physicochemical and structural insights into lyophilized mRNA-LNP from lyoprotectant and buffer screenings. J. Control. Release 373, 727\u2013737 (2024).","journal-title":"J. Control. Release"},{"key":"3331_CR21","doi-asserted-by":"publisher","first-page":"4327","DOI":"10.1039\/D2BM02031A","volume":"11","author":"A Lamoot","year":"2023","unstructured":"Lamoot, A. et al. Successful batch and continuous lyophilization of mRNA LNP formulations depend on cryoprotectants and ionizable lipids. Biomater. Sci. 11, 4327\u20134334 (2023).","journal-title":"Biomater. Sci."},{"key":"3331_CR22","doi-asserted-by":"publisher","first-page":"2256","DOI":"10.1007\/s13346-025-01964-z","volume":"16","author":"SH Sakers","year":"2025","unstructured":"Sakers, S. H. et al. Development of a microneedle patch for delivery of mRNA-lipid nanoparticles. Drug Deliv. Transl. Res. 16, 2256\u20132271 (2025).","journal-title":"Drug Deliv. Transl. Res."},{"key":"3331_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpb.2025.114819","volume":"215","author":"SH Sakers","year":"2025","unstructured":"Sakers, S. H. et al. The effect of mRNA-lipid nanoparticle composition on stability during microneedle patch manufacturing. Eur. J. Pharm. Biopharm. 215, 114819 (2025).","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"3331_CR24","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.jhealeco.2016.01.012","volume":"47","author":"JA DiMasi","year":"2016","unstructured":"DiMasi, J. A., Grabowski, H. G. & Hansen, R. W. Innovation in the pharmaceutical industry: new estimates of R&D costs. J. Health Econ. 47, 20\u201333 (2016).","journal-title":"J. Health Econ."},{"key":"3331_CR25","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1038\/549445a","volume":"549","author":"A Mullard","year":"2017","unstructured":"Mullard, A. The drug-maker\u2019s guide to the galaxy. Nature 549, 445\u2013447 (2017).","journal-title":"Nature"},{"key":"3331_CR26","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/s41591-024-03434-4","volume":"31","author":"K Zhang","year":"2025","unstructured":"Zhang, K. et al. Artificial intelligence in drug development. Nat. Med. 31, 45\u201359 (2025).","journal-title":"Nat. Med."},{"key":"3331_CR27","doi-asserted-by":"publisher","first-page":"305","DOI":"10.2147\/IJN.S123062","volume":"12","author":"RL Ball","year":"2017","unstructured":"Ball, R. L., Bajaj, P. & Whitehead, K. A. Achieving long-term stability of lipid nanoparticles: examining the effect of pH, temperature, and lyophilization. Int. J. Nanomedicine 12, 305\u2013315 (2017).","journal-title":"Int. J. Nanomedicine"},{"key":"3331_CR28","unstructured":"Reis, F. R. Vacuum Drying for Extending Food Shelf-Life (Springer, 2014)."},{"key":"3331_CR29","doi-asserted-by":"publisher","first-page":"2673","DOI":"10.1002\/jps.23998","volume":"103","author":"RH Walters","year":"2014","unstructured":"Walters, R. H. et al. Next generation drying technologies for pharmaceutical applications. J. Pharm. Sci. 103, 2673\u20132695 (2014).","journal-title":"J. Pharm. Sci."},{"key":"3331_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42948-2","volume":"14","author":"T Wei","year":"2023","unstructured":"Wei, T. et al. Lung SORT LNPs enable precise homology-directed repair mediated CRISPR\/Cas genome correction in cystic fibrosis models. Nat. Commun. 14, 7322 (2023).","journal-title":"Nat. Commun."},{"key":"3331_CR31","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":"3331_CR32","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1038\/s41565-023-01548-3","volume":"19","author":"AY Jiang","year":"2024","unstructured":"Jiang, A. Y. et al. Combinatorial development of nebulized mRNA delivery formulations for the lungs. Nat. Nanotechnol. 19, 364\u2013375 (2024).","journal-title":"Nat. Nanotechnol."},{"key":"3331_CR33","doi-asserted-by":"crossref","unstructured":"Doan, T. N. K., Davis, M. M. & Croyle, M. A. Identification of film-based formulations that move mRNA lipid nanoparticles out of the freezer. Mol. Ther. Nucleic Acids 35, 102179 (2024).","DOI":"10.1016\/j.omtn.2024.102179"},{"key":"3331_CR34","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aau6753","volume":"11","author":"D Reker","year":"2019","unstructured":"Reker, D. et al. \u2018Inactive\u2019 ingredients in oral medications. Sci. Transl. Med. 11, eaau6753 (2019).","journal-title":"Sci. Transl. Med."},{"key":"3331_CR35","doi-asserted-by":"publisher","first-page":"e0235076","DOI":"10.1371\/journal.pone.0235076","volume":"15","author":"Y Ionova","year":"2020","unstructured":"Ionova, Y. & Wilson, L. Biologic excipients: importance of clinical awareness of inactive ingredients. PLoS ONE 15, e0235076 (2020).","journal-title":"PLoS ONE"},{"key":"3331_CR36","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1109\/JPROC.2015.2494218","volume":"104","author":"B Shahriari","year":"2015","unstructured":"Shahriari, B., Swersky, K., Wang, Z., Adams, R. P. & De Freitas, N. Taking the human out of the loop: a review of Bayesian optimization. Proc. IEEE 104, 148\u2013175 (2015).","journal-title":"Proc. IEEE"},{"key":"3331_CR37","unstructured":"Tian, Y. et al. AutODEx: automated optimal design of experiments platform with data-and time-efficient multi-objective optimization. In NeurIPS 2023 Workshop on Adaptive Experimental Design and Active Learning in the Real World https:\/\/openreview.net\/forum?id=YrAXARes9d (2023)."},{"key":"3331_CR38","unstructured":"Tian, Y. et al. AutODEx: automated optimal design of experiments platform with data- and time-efficient multi-objective optimization. https:\/\/autodex.csail.mit.edu\/ (2023)."},{"key":"3331_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-023-00751-6","volume":"8","author":"L Zhang","year":"2023","unstructured":"Zhang, L. et al. Effect of mRNA-LNP components of two globally-marketed COVID-19 vaccines on efficacy and stability. NPJ Vaccines 8, 156 (2023).","journal-title":"NPJ Vaccines"},{"key":"3331_CR40","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1007\/s10898-020-00923-x","volume":"78","author":"D Zhan","year":"2020","unstructured":"Zhan, D. & Xing, H. Expected improvement for expensive optimization: a review. J. Glob. Optim. 78, 507\u2013544 (2020).","journal-title":"J. Glob. Optim."},{"key":"3331_CR41","doi-asserted-by":"publisher","unstructured":"Tian, J. Datasets for accelerated discovery of thermostable vaccines using data-efficient AI. Zenodo https:\/\/doi.org\/10.5281\/zenodo.21726997 (2026).","DOI":"10.5281\/zenodo.21726997"},{"key":"3331_CR42","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202303370","volume":"35","author":"MHY Cheng","year":"2023","unstructured":"Cheng, M. H. Y. et al. Induction of bleb structures in lipid nanoparticle formulations of mRNA leads to improved transfection potency. Adv. Mater. 35, 2303370 (2023).","journal-title":"Adv. Mater."},{"key":"3331_CR43","unstructured":"Daristotle, J., Vander Straeten, A., Langer, R. & Jaklenec, A. Synthetic construct SARS-CoV-2 vaccine receptor binding domain gene. GenBank https:\/\/www.ncbi.nlm.nih.gov\/nuccore\/OP839194 (2023)."},{"key":"3331_CR44","doi-asserted-by":"publisher","first-page":"121115","DOI":"10.1016\/j.ijpharm.2021.121115","volume":"609","author":"A Sharma","year":"2021","unstructured":"Sharma, A., Khamar, D., Cullen, S., Hayden, A. & Hughes, H. Innovative drying technologies for biopharmaceuticals. Int. J. Pharm. 609, 121115 (2021).","journal-title":"Int. J. Pharm."},{"key":"3331_CR45","unstructured":"Lutzmayer, S., Osoianu, E. &, Rosenfeld, T. Tip of the iceberg: economic and environmental impact of the vaccine cold chain. https:\/\/www.iqvia.com\/locations\/emea\/library\/white-papers\/tip-of-the-iceberg-economic-and-environmental-impact-of-the-vaccine-cold-chain (2025)."},{"key":"3331_CR46","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abj5505","volume":"7","author":"CB Wahl","year":"2024","unstructured":"Wahl, C. B. et al. Machine learning\u2013accelerated design and synthesis of polyelemental heterostructures. Sci. Adv. 7, eabj5505 (2024).","journal-title":"Sci. Adv."},{"key":"3331_CR47","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abf7435","volume":"7","author":"T Erps","year":"2021","unstructured":"Erps, T. et al. Accelerated discovery of 3D printing materials using data-driven multiobjective optimization. Sci. Adv. 7, eabf7435 (2021).","journal-title":"Sci. Adv."},{"key":"3331_CR48","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1177\/0300985817738095","volume":"55","author":"M Sedic","year":"2018","unstructured":"Sedic, M. et al. Safety evaluation of lipid nanoparticle\u2013formulated modified mRNA in the Sprague-Dawley rat and cynomolgus monkey. Vet. Pathol. 55, 341\u2013354 (2018).","journal-title":"Vet. Pathol."},{"key":"3331_CR49","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.jconrel.2006.04.014","volume":"114","author":"H Lv","year":"2006","unstructured":"Lv, H., Zhang, S., Wang, B., Cui, S. & Yan, J. Toxicity of cationic lipids and cationic polymers in gene delivery. J. Control. Release 114, 100\u2013109 (2006).","journal-title":"J. Control. Release"},{"key":"3331_CR50","doi-asserted-by":"publisher","first-page":"6867","DOI":"10.1016\/j.biomaterials.2010.05.027","volume":"31","author":"R Kedmi","year":"2010","unstructured":"Kedmi, R., Ben-Arie, N. & Peer, D. The systemic toxicity of positively charged lipid nanoparticles and the role of Toll-like receptor 4 in immune activation. Biomaterials 31, 6867\u20136875 (2010).","journal-title":"Biomaterials"},{"key":"3331_CR51","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201904905","volume":"32","author":"MP Lokugamage","year":"2020","unstructured":"Lokugamage, M. P. et al. Mild innate immune activation overrides efficient nanoparticle-mediated RNA delivery. Adv. Mater. 32, 1904905 (2020).","journal-title":"Adv. Mater."},{"key":"3331_CR52","doi-asserted-by":"publisher","first-page":"159318","DOI":"10.1016\/j.cej.2025.159318","volume":"505","author":"D Chen","year":"2025","unstructured":"Chen, D. et al. Controlled preparation of lipid nanoparticles in microreactors: mixing time, morphology and mRNA delivery. Chem. Eng. J. 505, 159318 (2025).","journal-title":"Chem. Eng. J."},{"key":"3331_CR53","doi-asserted-by":"publisher","first-page":"21206","DOI":"10.1021\/acsnano.4c18274","volume":"19","author":"A Udepurkar","year":"2025","unstructured":"Udepurkar, A. et al. Structure and morphology of lipid nanoparticles for nucleic acid drug delivery: a review. ACS Nano 19, 21206\u201321242 (2025).","journal-title":"ACS Nano"},{"key":"3331_CR54","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1016\/j.jconrel.2024.07.046","volume":"373","author":"JB Simonsen","year":"2024","unstructured":"Simonsen, J. B. A perspective on bleb and empty LNP structures. J. Control. Release 373, 952\u2013961 (2024).","journal-title":"J. Control. Release"},{"key":"3331_CR55","doi-asserted-by":"publisher","unstructured":"Garnett, R. Modeling with Gaussian processes. In Bayesian Optimization (ed. Garnett, R.) 45\u221266 https:\/\/doi.org\/10.1017\/9781108348973.004 (Cambridge Univ. Press, 2023).","DOI":"10.1017\/9781108348973.004"},{"key":"3331_CR56","doi-asserted-by":"publisher","unstructured":"Garnett, R. Common Bayesian optimization policies. In Bayesian Optimization (ed. Garnett, R.) 123\u2212156 https:\/\/doi.org\/10.1017\/9781108348973.008 (Cambridge Univ. Press, 2023).","DOI":"10.1017\/9781108348973.008"},{"key":"3331_CR57","unstructured":"Tian, Y. AutoOED: automated optimal experimental design platform. https:\/\/github.com\/yunshengtian\/AutoOED.git (2021)."}],"container-title":["Nature Biotechnology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41587-026-03331-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41587-026-03331-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41587-026-03331-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T09:42:41Z","timestamp":1790588561000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41587-026-03331-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,28]]},"references-count":57,"alternative-id":["3331"],"URL":"https:\/\/doi.org\/10.1038\/s41587-026-03331-w","relation":{},"ISSN":["1087-0156","1546-1696"],"issn-type":[{"value":"1087-0156","type":"print"},{"value":"1546-1696","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,28]]},"assertion":[{"value":"13 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"From Fiscal Year 2020 to the present, A.J. receives licensing fees (for patents on which she was an inventor) from, has investments in, consults (or was on Scientific Advisory Boards or Boards of Directors) for, lectured (and received a fee) or conducts sponsored research at MIT for which she was not paid for the following entities: The Est\u00e9e Lauder Companies, Moderna Therapeutics, OmniPulse Biosciences, Particles for Humanity, SiO2 Materials Science and VitaKey. From Fiscal Year 2020 to the present, R.S.L. receives licensing fees (for patents on which he was an inventor) from, has investments in, consults (or was on Scientific Advisory Boards or Boards of Directors) for, lectured (and received a fee) or conducts sponsored research at MIT for which he was not paid for the following entities:\n                      \n                      . The remaining authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}