{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T03:01:37Z","timestamp":1781665297724,"version":"3.54.5"},"reference-count":40,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"NIH","award":["R01 CA224605"],"award-info":[{"award-number":["R01 CA224605"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Nucleic acid therapeutics and gene delivery platforms have the potential to change the way we treat disease, enabling precision medicine. Advances in biotechnology have allowed for production of virtually any functional protein or peptide in the human body through the introduction of various classes of RNA, including regulatory and coding RNAs (e.g., mRNA) in the form of linear or circular RNA (circRNA). To be effective, nucleic acid therapeutics require safe, stable, and efficient delivery vehicles that protect the otherwise labile cargo from degradation, promote cellular uptake, and facilitate payload release. Lipid nanoparticles (LNPs) have enjoyed recent clinical success for the delivery of mRNA to combat disease \u2013 especially against coronavirus 2019 (SARS CoV-2) and, more recently, against high-grade ductal breast carcinoma (clinical trial) \u2013 marking significant milestones for RNA nanomedicines. As an alternative to LNPs and mammalian viral vectors, we report the use of nucleoprotein components from a filamentous plant virus, potato virus X (PVX) as an RNA platform delivery technology. Designer nucleoprotein complexes of filamentous and halo-shaped nanoparticles were obtained through self-assembled templating on custom mRNAs and circRNAs. The flexuous nature of the PVX platform enabled the packing of circRNA yielding a unique nanoparticle platform. We explored assembly from coat protein (CP) obtained from PVX particles produced in planta but also extended the design space by producing recombinant CP by bacterial expression. Controlled mixed assemblies were achieved allowing the programming of mosaic particles with integrated functionality; length control was also demonstrated, resulting in bespoke nucleic acid delivery vehicles for tunable pharmacology. Using reporter genes, we demonstrate successful transfection of eukaryotic cells and target protein expression.<\/jats:p>","DOI":"10.1038\/s41598-025-27488-7","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T11:13:45Z","timestamp":1765538025000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Engineering filamentous potato virus X as a platform nanotechnology for nucleic acid gene delivery"],"prefix":"10.1038","volume":"15","author":[{"given":"Bryan","family":"Duoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krister J.","family":"Barkovich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Schuphan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashant","family":"Mali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole F.","family":"Steinmetz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,12]]},"reference":[{"issue":"10","key":"27488_CR1","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1038\/s41565-022-01174-5","volume":"17","author":"X Huang","year":"2022","unstructured":"Huang, X. et al. Nanotechnology-based strategies against SARS-CoV-2 variants. Nat. Nanotechnol. 17 (10), 1027\u20131037. https:\/\/doi.org\/10.1038\/s41565-022-01174-5 (2022).","journal-title":"Nat. Nanotechnol."},{"issue":"1","key":"27488_CR2","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1038\/s41392-022-01007-w","volume":"7","author":"S Qin","year":"2022","unstructured":"Qin, S. et al. mRNA-based therapeutics: powerful and versatile tools to combat diseases. Signal. Transduct. Target. Therapy. 7 (1), 166. https:\/\/doi.org\/10.1038\/s41392-022-01007-w (2022).","journal-title":"Signal. Transduct. Target. Therapy"},{"issue":"11","key":"27488_CR3","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 (11), 1586\u20131600. https:\/\/doi.org\/10.1038\/s41587-022-01491-z (2022).","journal-title":"Nat. Biotechnol."},{"issue":"6","key":"27488_CR4","doi-asserted-by":"publisher","first-page":"1272","DOI":"10.1038\/s12276-024-01220-3","volume":"56","author":"HJ Hwang","year":"2024","unstructured":"Hwang, H. J. & Kim, Y. K. Molecular mechanisms of circular RNA translation. Exp. Mol. Med. 56 (6), 1272\u20131280. https:\/\/doi.org\/10.1038\/s12276-024-01220-3 (2024).","journal-title":"Exp. Mol. Med."},{"issue":"1","key":"27488_CR5","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.virol.2013.03.001","volume":"441","author":"O Azizgolshani","year":"2013","unstructured":"Azizgolshani, O., Garmann, R. F., Cadena-Nava, R., Knobler, C. M. & Gelbart, W. M. Reconstituted plant viral capsids can release genes to mammalian cells. Virology 441 (1), 12\u201317. https:\/\/doi.org\/10.1016\/j.virol.2013.03.001 (2013).","journal-title":"Virology"},{"key":"27488_CR6","doi-asserted-by":"publisher","unstructured":"Lam, P. & Steinmetz, N. F. Plant viral and bacteriophage delivery of nucleic acid therapeutics. Wiley interdisciplinary reviews. Nanomed. Nanobiotechnol. 10 (1). https:\/\/doi.org\/10.1002\/wnan.1487 (2018).","DOI":"10.1002\/wnan.1487"},{"issue":"1","key":"27488_CR7","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.virol.2005.01.018","volume":"334","author":"SJ Kwon","year":"2005","unstructured":"Kwon, S. J. et al. cis-Acting sequences required for coat protein binding and in vitro assembly of potato virus X. Virology 334 (1), 83\u201397. https:\/\/doi.org\/10.1016\/j.virol.2005.01.018 (2005).","journal-title":"Virology"},{"issue":"4","key":"27488_CR8","doi-asserted-by":"publisher","first-page":"359","DOI":"10.3390\/vaccines9040359","volume":"9","author":"TTH Thi","year":"2021","unstructured":"Thi, T. T. H. et al. Lipid-Based nanoparticles in the clinic and clinical trials: from cancer nanomedicine to COVID-19 vaccines. Vaccines 9 (4), 359. https:\/\/doi.org\/10.3390\/vaccines9040359 (2021).","journal-title":"Vaccines"},{"key":"27488_CR9","doi-asserted-by":"publisher","first-page":"1296091","DOI":"10.3389\/fonc.2024.1296091","volume":"14","author":"I Waheed","year":"2024","unstructured":"Waheed, I. et al. Lipid-based nanoparticles as drug delivery carriers for cancer therapy. Front. Oncol. 14, 1296091. https:\/\/doi.org\/10.3389\/fonc.2024.1296091 (2024).","journal-title":"Front. Oncol."},{"issue":"5","key":"27488_CR10","doi-asserted-by":"publisher","first-page":"1792","DOI":"10.1016\/j.ymthe.2022.04.004","volume":"30","author":"RE Young","year":"2022","unstructured":"Young, R. E., Hofbauer, S. I. & Riley, R. S. Overcoming the challenge of long-term storage of mRNA-lipid nanoparticle vaccines. Mol. Therapy: J. Am. Soc. Gene Therapy. 30 (5), 1792\u20131793. https:\/\/doi.org\/10.1016\/j.ymthe.2022.04.004 (2022).","journal-title":"Mol. Therapy: J. Am. Soc. Gene Therapy"},{"issue":"12","key":"27488_CR11","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1038\/s41578-021-00358-0","volume":"6","author":"X Hou","year":"2021","unstructured":"Hou, X., Zaks, T., Langer, R. & Dong, Y. Lipid nanoparticles for mRNA delivery. Nat. Reviews Mater. 6 (12), 1078\u20131094. https:\/\/doi.org\/10.1038\/s41578-021-00358-0 (2021).","journal-title":"Nat. Reviews Mater."},{"issue":"1","key":"27488_CR12","doi-asserted-by":"publisher","first-page":"5354","DOI":"10.1038\/s41467-025-60959-z","volume":"16","author":"JM Johansson","year":"2025","unstructured":"Johansson, J. M. et al. Cellular and biophysical barriers to lipid nanoparticle mediated delivery of RNA to the cytosol. Nat. Commun. 16 (1), 5354. https:\/\/doi.org\/10.1038\/s41467-025-60959-z (2025).","journal-title":"Nat. Commun."},{"issue":"6","key":"27488_CR13","doi-asserted-by":"publisher","first-page":"109804","DOI":"10.1016\/j.isci.2024.109804","volume":"27","author":"T Zhang","year":"2024","unstructured":"Zhang, T. et al. Optimized lipid nanoparticles (LNPs) for organ-selective nucleic acids delivery in vivo. iScience 27 (6), 109804. https:\/\/doi.org\/10.1016\/j.isci.2024.109804 (2024).","journal-title":"iScience"},{"key":"27488_CR14","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1146\/annurev-med-012017-043332","volume":"70","author":"XM Anguela","year":"2019","unstructured":"Anguela, X. M. & High, K. A. Entering the modern era of gene therapy. Annu. Rev. Med. 70, 273\u2013288. https:\/\/doi.org\/10.1146\/annurev-med-012017-043332 (2019).","journal-title":"Annu. Rev. Med."},{"issue":"4","key":"27488_CR15","doi-asserted-by":"publisher","first-page":"816","DOI":"10.1039\/d2tb02199d","volume":"11","author":"SK Chan","year":"2023","unstructured":"Chan, S. K. & Steinmetz, N. F. microRNA-181a Silencing by antisense oligonucleotides delivered by virus-like particles. J. Mater. Chem. B. 11 (4), 816\u2013825. https:\/\/doi.org\/10.1039\/d2tb02199d (2023).","journal-title":"J. Mater. Chem. B"},{"issue":"6","key":"27488_CR16","doi-asserted-by":"publisher","first-page":"2727","DOI":"10.1021\/acs.molpharmaceut.3c01105","volume":"21","author":"S Karan","year":"2024","unstructured":"Karan, S. et al. Vivo delivery of spherical and cylindrical in vitro reconstituted Virus-like particles containing the same Self-Amplifying mRNA. Mol. Pharm. 21 (6), 2727\u20132739. https:\/\/doi.org\/10.1021\/acs.molpharmaceut.3c01105 (2024).","journal-title":"Mol. Pharm."},{"issue":"5","key":"27488_CR17","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1038\/s41589-020-0502-4","volume":"16","author":"A Grinzato","year":"2020","unstructured":"Grinzato, A. et al. Atomic structure of potato virus X, the prototype of the alphaflexiviridae family. Nat. Chem. Biol. 16 (5), 564\u2013569. https:\/\/doi.org\/10.1038\/s41589-020-0502-4 (2020).","journal-title":"Nat. Chem. Biol."},{"key":"27488_CR18","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/978-1-62703-751-8_1","volume":"1108","author":"KL Lee","year":"2014","unstructured":"Lee, K. L., Uhde-Holzem, K., Fischer, R., Commandeur, U. & Steinmetz, N. F. Genetic engineering and chemical conjugation of potato virus X. Methods Mol. Biology (Clifton N J). 1108, 3\u201321. https:\/\/doi.org\/10.1007\/978-1-62703-751-8_1 (2014).","journal-title":"Methods Mol. Biology (Clifton N J)"},{"issue":"3","key":"27488_CR19","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1111\/mpp.13163","volume":"23","author":"J Verchot","year":"2022","unstructured":"Verchot, J. Potato virus X: A global potato-infecting virus and type member of the potexvirus genus. Mol. Plant Pathol. 23 (3), 315\u2013320. https:\/\/doi.org\/10.1111\/mpp.13163 (2022).","journal-title":"Mol. Plant Pathol."},{"issue":"5","key":"27488_CR20","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1111\/j.1364-3703.2007.00420.x","volume":"8","author":"J Atabekov","year":"2007","unstructured":"Atabekov, J., Dobrov, E., Karpova, O. & Rodionova, N. Potato virus X: structure, disassembly and reconstitution. Mol. Plant Pathol. 8 (5), 667\u2013675. https:\/\/doi.org\/10.1111\/j.1364-3703.2007.00420.x (2007).","journal-title":"Mol. Plant Pathol."},{"issue":"6","key":"27488_CR21","doi-asserted-by":"publisher","first-page":"2348","DOI":"10.1039\/c6nr09099k","volume":"9","author":"DH Le","year":"2017","unstructured":"Le, D. H., Lee, K. L., Shukla, S., Commandeur, U. & Steinmetz, N. F. Potato virus X, a filamentous plant viral nanoparticle for doxorubicin delivery in cancer therapy. Nanoscale 9 (6), 2348\u20132357. https:\/\/doi.org\/10.1039\/c6nr09099k (2017).","journal-title":"Nanoscale"},{"issue":"10","key":"27488_CR22","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1038\/nnano.2007.299","volume":"2","author":"M Comellas-Aragon\u00e8s","year":"2007","unstructured":"Comellas-Aragon\u00e8s, M. et al. A virus-based single-enzyme nanoreactor. Nat. Nanotechnol. 2 (10), 635\u2013639. https:\/\/doi.org\/10.1038\/nnano.2007.299 (2007).","journal-title":"Nat. Nanotechnol."},{"key":"27488_CR23","doi-asserted-by":"publisher","unstructured":"R\u00f6der, J., Fischer, R. & Commandeur, U. Engineering potato virus X particles for a covalent protein based attachment of Enzymes. Small (Weinheim an der Bergstrasse. Germany) 13 (48). https:\/\/doi.org\/10.1002\/smll.201702151 (2017).","DOI":"10.1002\/smll.201702151"},{"issue":"16","key":"27488_CR24","doi-asserted-by":"publisher","first-page":"e2304243","DOI":"10.1002\/adhm.202304243","volume":"13","author":"J Schuphan","year":"2024","unstructured":"Schuphan, J. et al. A combination of flexible modified plant virus nanoparticles enables additive effects resulting in improved osteogenesis. Adv. Healthc. Mater. 13 (16), e2304243. https:\/\/doi.org\/10.1002\/adhm.202304243 (2024).","journal-title":"Adv. Healthc. Mater."},{"issue":"2","key":"27488_CR25","doi-asserted-by":"publisher","first-page":"e0118096","DOI":"10.1371\/journal.pone.0118096","volume":"10","author":"J Jobsri","year":"2015","unstructured":"Jobsri, J. et al. Plant virus particles carrying tumour antigen activate TLR7 and induce high levels of protective antibody. PloS One. 10 (2), e0118096. https:\/\/doi.org\/10.1371\/journal.pone.0118096 (2015).","journal-title":"PloS One"},{"issue":"4","key":"27488_CR26","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1208\/s12248-021-00608-7","volume":"23","author":"H Zu","year":"2021","unstructured":"Zu, H. & Gao, D. Non-viral vectors in gene therapy: recent Development, Challenges, and prospects. AAPS J. 23 (4), 78. https:\/\/doi.org\/10.1208\/s12248-021-00608-7 (2021).","journal-title":"AAPS J."},{"issue":"8","key":"27488_CR27","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1111\/pbi.12478","volume":"13","author":"H Daniell","year":"2015","unstructured":"Daniell, H., Streatfield, S. J. & Rybicki, E. P. Advances in molecular farming: key technologies, scaled up production and lead targets. Plant Biotechnol. J. 13 (8), 1011\u20131012. https:\/\/doi.org\/10.1111\/pbi.12478 (2015).","journal-title":"Plant Biotechnol. J."},{"key":"27488_CR28","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.copbio.2019.11.005","volume":"61","author":"TL Tsekoa","year":"2020","unstructured":"Tsekoa, T. L., Singh, A. A. & Buthelezi, S. G. Molecular farming for therapies and vaccines in Africa. Curr. Opin. Biotechnol. 61, 89\u201395. https:\/\/doi.org\/10.1016\/j.copbio.2019.11.005 (2020).","journal-title":"Curr. Opin. Biotechnol."},{"key":"27488_CR29","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.omtn.2019.02.018","volume":"15","author":"M Baiersd\u00f6rfer","year":"2019","unstructured":"Baiersd\u00f6rfer, M. et al. A facile method for the removal of DsRNA contaminant from in Vitro-Transcribed mRNA. Mol. Therapy Nucleic Acids. 15, 26\u201335. https:\/\/doi.org\/10.1016\/j.omtn.2019.02.018 (2019).","journal-title":"Mol. Therapy Nucleic Acids"},{"issue":"4","key":"27488_CR30","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1038\/nnano.2007.76","volume":"2","author":"N Carette","year":"2007","unstructured":"Carette, N. et al. A virus-based biocatalyst. Nat. Nanotechnol. 2 (4), 226\u2013229. https:\/\/doi.org\/10.1038\/nnano.2007.76 (2007).","journal-title":"Nat. Nanotechnol."},{"issue":"2","key":"27488_CR31","doi-asserted-by":"publisher","first-page":"2501","DOI":"10.1021\/acsnano.8b09462","volume":"13","author":"DHT Le","year":"2019","unstructured":"Le, D. H. T., Commandeur, U. & Steinmetz, N. F. Presentation and delivery of tumor necrosis Factor-Related Apoptosis-Inducing ligand via elongated plant viral nanoparticle enhances antitumor efficacy. ACS Nano. 13 (2), 2501\u20132510. https:\/\/doi.org\/10.1021\/acsnano.8b09462 (2019).","journal-title":"ACS Nano"},{"issue":"1","key":"27488_CR32","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1038\/s41551-024-01245-z","volume":"9","author":"M Tong","year":"2025","unstructured":"Tong, M. et al. Robust genome and cell engineering via in vitro and in situ circularized RNAs. Nat. Biomedical Eng. 9 (1), 109\u2013126. https:\/\/doi.org\/10.1038\/s41551-024-01245-z (2025).","journal-title":"Nat. Biomedical Eng."},{"issue":"3","key":"27488_CR33","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.1093\/nar\/gkt1053","volume":"42","author":"BA McNeil","year":"2014","unstructured":"McNeil, B. A., Simon, D. M. & Zimmerly, S. Alternative splicing of a group II intron in a surface layer protein gene in clostridium Tetani. Nucleic Acids Res. 42 (3), 1959\u20131969. https:\/\/doi.org\/10.1093\/nar\/gkt1053 (2014).","journal-title":"Nucleic Acids Res."},{"key":"27488_CR34","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1146\/annurev-biophys-062215-011149","volume":"45","author":"AM Pyle","year":"2016","unstructured":"Pyle, A. M. Group II intron Self-Splicing. Annual Rev. Biophys. 45, 183\u2013205. https:\/\/doi.org\/10.1146\/annurev-biophys-062215-011149 (2016).","journal-title":"Annual Rev. Biophys."},{"key":"27488_CR35","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13100-015-0037-5","volume":"6","author":"S Zimmerly","year":"2015","unstructured":"Zimmerly, S. & Semper, C. Evolution of group II introns. Mob. DNA. 6, 7. https:\/\/doi.org\/10.1186\/s13100-015-0037-5 (2015).","journal-title":"Mob. DNA"},{"key":"27488_CR36","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.addr.2018.08.007","volume":"145","author":"I Balke","year":"2019","unstructured":"Balke, I. & Zeltins, A. Use of plant viruses and virus-like particles for the creation of novel vaccines. Adv. Drug Deliv. Rev. 145, 119\u2013129. https:\/\/doi.org\/10.1016\/j.addr.2018.08.007 (2019).","journal-title":"Adv. Drug Deliv. Rev."},{"issue":"20","key":"27488_CR37","doi-asserted-by":"publisher","first-page":"e1907150","DOI":"10.1002\/smll.201907150","volume":"16","author":"C Wang","year":"2020","unstructured":"Wang, C. et al. Active delivery of VLPs promotes Anti-Tumor activity in a mouse ovarian tumor model. Small (Weinheim Der Bergstrasse Germany). 16 (20), e1907150. https:\/\/doi.org\/10.1002\/smll.201907150 (2020).","journal-title":"Small (Weinheim Der Bergstrasse Germany)"},{"issue":"43","key":"27488_CR38","doi-asserted-by":"publisher","first-page":"e2221859120","DOI":"10.1073\/pnas.2221859120","volume":"120","author":"YH Chung","year":"2023","unstructured":"Chung, Y. H. et al. Viral nanoparticle vaccines against S100A9 reduce lung tumor seeding and metastasis. Proc. Natl. Acad. Sci. U.S.A. 120 (43), e2221859120. https:\/\/doi.org\/10.1073\/pnas.2221859120 (2023).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"issue":"2","key":"27488_CR39","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1128\/JVI.01811-07","volume":"82","author":"P Lacasse","year":"2008","unstructured":"Lacasse, P., Denis, J., Lapointe, R., Leclerc, D. & Lamarre, A. Novel plant virus-based vaccine induces protective cytotoxic T-lymphocyte-mediated antiviral immunity through dendritic cell maturation. J. Virol. 82 (2), 785\u2013794. https:\/\/doi.org\/10.1128\/JVI.01811-07 (2008).","journal-title":"J. Virol."},{"issue":"14","key":"27488_CR40","doi-asserted-by":"publisher","first-page":"3935","DOI":"10.1039\/d0bm00683a","volume":"8","author":"S Shukla","year":"2020","unstructured":"Shukla, S. et al. Affinity of plant viral nanoparticle potato virus X (PVX) towards malignant B cells enables cancer drug delivery. Biomaterials Sci. 8 (14), 3935\u20133943. https:\/\/doi.org\/10.1039\/d0bm00683a (2020).","journal-title":"Biomaterials Sci."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-27488-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-27488-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-27488-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T11:13:56Z","timestamp":1765538036000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-27488-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,12]]},"references-count":40,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["27488"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-27488-7","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,12]]},"assertion":[{"value":"14 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare the following competing financial interest(s): Dr. Steinmetz is a co-founder and CEO of, and has equity in, PlantiosX Inc. Dr. Steinmetz is a co-founder of, and has equity in, Mosaic ImmunoEngineering, Inc. Dr. Steinmetz is a co-founder and manager of Pokometz Scientific LLC, under which she is a paid consultant to Ring Therapeutics, Inc. Dr. Mali is a scientific co-founder of Shape Therapeutics, Navega Therapeutics, Pi Bio, Boundless Biosciences, and Engine Biosciences. The terms of these arrangements have been reviewed and approved by the University of California, San Diego in accordance with its conflict of interest policies.\u00a0The other authors declare no potential COI.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"43714"}}