{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T23:57:44Z","timestamp":1779926264486,"version":"3.53.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":24,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001349","name":"National Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001349","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-35611-5","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T14:24:46Z","timestamp":1768227886000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Influenza A virus derived NS1 enhances translation of HPLC purified mRNA and interferon adjuvanted mRNA vaccination"],"prefix":"10.1038","volume":"16","author":[{"given":"Kyle K. L.","family":"Phua","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jas-Min","family":"Chin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Wen","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Pardi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Smita K.","family":"Nair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,12]]},"reference":[{"issue":"3","key":"35611_CR1","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.jconrel.2012.12.029","volume":"166","author":"KK Phua","year":"2013","unstructured":"Phua, K. K., Leong, K. W. & Nair, S. K. Transfection efficiency and transgene expression kinetics of mRNA delivered in naked and nanoparticle format. J. Control Release. 166 (3), 227\u2013233 (2013).","journal-title":"J. Control Release"},{"issue":"5","key":"35611_CR2","doi-asserted-by":"publisher","first-page":"315","DOI":"10.3109\/1061186X.2010.504262","volume":"19","author":"F Perche","year":"2011","unstructured":"Perche, F. et al. Selective gene delivery in dendritic cells with mannosylated and histidylated lipopolyplexes. J. Drug Target. 19 (5), 315\u2013325 (2011).","journal-title":"J. Drug Target."},{"key":"35611_CR3","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.jconrel.2015.08.007","volume":"217","author":"N Pardi","year":"2015","unstructured":"Pardi, N. et al. Expression kinetics of nucleoside-modified mRNA delivered in lipid nanoparticles to mice by various routes. J. Control Release. 217, 345\u2013351 (2015).","journal-title":"J. Control Release"},{"key":"35611_CR4","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.jconrel.2015.12.032","volume":"240","author":"KJ Kauffman","year":"2016","unstructured":"Kauffman, K. J., Webber, M. J. & Anderson, D. G. Materials for non-viral intracellular delivery of messenger RNA therapeutics. J. Control Release. 240, 227\u2013234 (2016).","journal-title":"J. Control Release"},{"key":"35611_CR5","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1016\/j.omtn.2018.03.005","volume":"11","author":"S Golombek","year":"2018","unstructured":"Golombek, S. et al. Intradermal delivery of synthetic mRNA using Hollow microneedles for efficient and rapid production of exogenous proteins in skin. Mol. Ther. Nucleic Acids. 11, 382\u2013392 (2018).","journal-title":"Mol. Ther. Nucleic Acids"},{"issue":"1","key":"35611_CR6","doi-asserted-by":"publisher","first-page":"11842","DOI":"10.1038\/s41598-018-30290-3","volume":"8","author":"KJ Koh","year":"2018","unstructured":"Koh, K. J. et al. Formulation, characterization and evaluation of mRNA-loaded dissolvable polymeric microneedles (RNApatch). Sci. Rep. 8 (1), 11842 (2018).","journal-title":"Sci. Rep."},{"issue":"9","key":"35611_CR7","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.1038\/mt.2015.103","volume":"23","author":"A Thess","year":"2015","unstructured":"Thess, A. et al. Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals. Mol. Ther. 23 (9), 1456\u20131464 (2015).","journal-title":"Mol. Ther."},{"key":"35611_CR8","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.omtn.2019.02.018","volume":"15","author":"M Baiersdorfer","year":"2019","unstructured":"Baiersdorfer, M. et al. A facile method for the removal of DsRNA contaminant from in Vitro-Transcribed mRNA. Mol. Ther. Nucleic Acids. 15, 26\u201335 (2019).","journal-title":"Mol. Ther. Nucleic Acids"},{"issue":"21","key":"35611_CR9","doi-asserted-by":"publisher","first-page":"e142","DOI":"10.1093\/nar\/gkr695","volume":"39","author":"K Kariko","year":"2011","unstructured":"Kariko, K. et al. Generating the optimal mRNA for therapy: HPLC purification eliminates immune activation and improves translation of nucleoside-modified, protein-encoding mRNA. Nucleic Acids Res. 39 (21), e142 (2011).","journal-title":"Nucleic Acids Res."},{"issue":"17","key":"35611_CR10","doi-asserted-by":"publisher","first-page":"5884","DOI":"10.1093\/nar\/gkq347","volume":"38","author":"BR Anderson","year":"2010","unstructured":"Anderson, B. R. et al. Incorporation of Pseudouridine into mRNA enhances translation by diminishing PKR activation. Nucleic Acids Res. 38 (17), 5884\u20135892 (2010).","journal-title":"Nucleic Acids Res."},{"key":"35611_CR11","doi-asserted-by":"crossref","unstructured":"Devoldere, J. et al. Evading innate immunity in nonviral mRNA delivery: don\u2019t shoot the messenger (Drug Discov Today, 2015).","DOI":"10.1016\/j.drudis.2015.07.009"},{"issue":"12B","key":"35611_CR12","doi-asserted-by":"publisher","first-page":"2580","DOI":"10.1101\/gad.6.12b.2580","volume":"6","author":"R Simon","year":"1992","unstructured":"Simon, R., Tassan, J. P. & Richter, J. D. Translational control by poly(A) elongation during xenopus development: differential repression and enhancement by a novel cytoplasmic polyadenylation element. Genes Dev. 6 (12B), 2580\u20132591 (1992).","journal-title":"Genes Dev."},{"key":"35611_CR13","doi-asserted-by":"crossref","unstructured":"Liu, Y. et al. Modulation of mRNA Translation and Cell Viability by Influenza A Virus Derived Nonstructural Protein 1 (Nucleic Acid Ther, 2018).","DOI":"10.1089\/nat.2017.0712"},{"issue":"1","key":"35611_CR14","doi-asserted-by":"publisher","first-page":"11972","DOI":"10.1038\/s41598-019-48559-6","volume":"9","author":"Y Liu","year":"2019","unstructured":"Liu, Y. et al. Messenger RNA translation enhancement by immune evasion proteins: a comparative study between EKB (vaccinia virus) and NS1 (influenza A virus). Sci. Rep. 9 (1), 11972 (2019).","journal-title":"Sci. Rep."},{"issue":"11","key":"35611_CR15","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1089\/hum.2015.045","volume":"26","author":"MA Poleganov","year":"2015","unstructured":"Poleganov, M. A. et al. Efficient reprogramming of human fibroblasts and Blood-Derived endothelial progenitor cells using nonmodified RNA for reprogramming and immune evasion. Hum. Gene Ther. 26 (11), 751\u2013766 (2015).","journal-title":"Hum. Gene Ther."},{"key":"35611_CR16","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.biomaterials.2017.04.009","volume":"133","author":"KKL Phua","year":"2017","unstructured":"Phua, K. K. L., Liu, Y. & Sim, S. H. Non-linear enhancement of mRNA delivery efficiencies by influenza A derived NS1 protein engendering host gene Inhibition property. Biomaterials 133, 29\u201336 (2017).","journal-title":"Biomaterials"},{"issue":"3","key":"35611_CR17","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1124\/jpet.104.078113","volume":"312","author":"SC Semple","year":"2005","unstructured":"Semple, S. C. et al. Immunogenicity and rapid blood clearance of liposomes containing polyethylene glycol-lipid conjugates and nucleic acid. J. Pharmacol. Exp. Ther. 312 (3), 1020\u20131026 (2005).","journal-title":"J. Pharmacol. Exp. Ther."},{"issue":"35","key":"35611_CR18","doi-asserted-by":"publisher","first-page":"13093","DOI":"10.1073\/pnas.0805213105","volume":"105","author":"K Das","year":"2008","unstructured":"Das, K. et al. Structural basis for suppression of a host antiviral response by influenza A virus. Proc. Natl. Acad. Sci. U S A. 105 (35), 13093\u201313098 (2008).","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"issue":"13","key":"35611_CR19","doi-asserted-by":"publisher","first-page":"6528","DOI":"10.1128\/JVI.00386-15","volume":"89","author":"DA Khaperskyy","year":"2015","unstructured":"Khaperskyy, D. A. & McCormick, C. Timing is everything: coordinated control of host shutoff by influenza A virus NS1 and PA-X proteins. J. Virol. 89 (13), 6528\u20136531 (2015).","journal-title":"J. Virol."},{"key":"35611_CR20","doi-asserted-by":"crossref","unstructured":"Nair, S., Archer, G. E. & Tedder, T. F. Isolation and generation of human dendritic cells. Curr. Protoc. Immunol. Chapter 7: p. Unit7 32. (2012)","DOI":"10.1002\/0471142735.im0732s99"},{"key":"35611_CR21","doi-asserted-by":"publisher","first-page":"e1187","DOI":"10.1038\/cddis.2014.101","volume":"5","author":"RL Huang","year":"2014","unstructured":"Huang, R. L. et al. Opposing TNF-alpha\/IL-1beta- and BMP-2-activated MAPK signaling pathways converge on Runx2 to regulate BMP-2-induced osteoblastic differentiation. Cell. Death Dis. 5, e1187 (2014).","journal-title":"Cell. Death Dis."},{"issue":"3","key":"35611_CR22","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/S1525-0016(03)00168-0","volume":"8","author":"ZY Chen","year":"2003","unstructured":"Chen, Z. Y. et al. Minicircle DNA vectors devoid of bacterial DNA result in persistent and high-level transgene expression in vivo. Mol. Ther. 8 (3), 495\u2013500 (2003).","journal-title":"Mol. Ther."},{"issue":"4","key":"35611_CR23","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.1021\/acs.jproteome.7b00815","volume":"17","author":"RL Kuo","year":"2018","unstructured":"Kuo, R. L. et al. Interactome analysis of NS1 protein encoded by influenza A H7N9 virus reveals an inhibitory role of NS1 in host mRNA maturation. J. Proteome Res. 17 (4), 1474\u20131484 (2018).","journal-title":"J. Proteome Res."},{"issue":"3","key":"35611_CR24","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.cell.2011.07.014","volume":"146","author":"L Salmena","year":"2011","unstructured":"Salmena, L. et al. A CeRNA hypothesis: the Rosetta stone of a hidden RNA language? Cell 146 (3), 353\u2013358 (2011).","journal-title":"Cell"},{"issue":"24","key":"35611_CR25","doi-asserted-by":"publisher","first-page":"11566","DOI":"10.1128\/JVI.74.24.11566-11573.2000","volume":"74","author":"X Wang","year":"2000","unstructured":"Wang, X. et al. Influenza A virus NS1 protein prevents activation of NF-kappaB and induction of alpha\/beta interferon. J. Virol. 74 (24), 11566\u201311573 (2000).","journal-title":"J. Virol."},{"issue":"11","key":"35611_CR26","doi-asserted-by":"publisher","first-page":"e13927","DOI":"10.1371\/journal.pone.0013927","volume":"5","author":"D Jia","year":"2010","unstructured":"Jia, D. et al. Influenza virus non-structural protein 1 (NS1) disrupts interferon signaling. PLoS One. 5 (11), e13927 (2010).","journal-title":"PLoS One"},{"key":"35611_CR27","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.jconrel.2017.09.041","volume":"266","author":"R Verbeke","year":"2017","unstructured":"Verbeke, R. et al. Co-delivery of nucleoside-modified mRNA and TLR agonists for cancer immunotherapy: restoring the immunogenicity of Immunosilent mRNA. J. Controlled Release. 266, 287\u2013300 (2017).","journal-title":"J. Controlled Release"},{"key":"35611_CR28","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1007\/978-1-62703-260-5_3","volume":"969","author":"D Weissman","year":"2013","unstructured":"Weissman, D. et al. HPLC purification of in vitro transcribed long RNA. Methods Mol. Biol. 969, 43\u201354 (2013).","journal-title":"Methods Mol. Biol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-35611-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-35611-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-35611-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T23:03:16Z","timestamp":1770332596000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-35611-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,12]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["35611"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-35611-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,12]]},"assertion":[{"value":"6 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 January 2026","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 no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Primary human cells used in these experiments were isolated from blood obtained from healthy human volunteers following informed written consent using a protocol approved by the Duke University Institutional Review Board and carried out in accordance with relevant guidelines and regulations. Prior to conducting the research described in this paper, the experimenters were trained in \u201cResponsible Care and Use of Laboratory Animals\u201d as required by the National Advisory Committee for Laboratory Animal Research (NACLAR) in Singapore. The facilities at National University of Singapore (NUS) are fully accredited by the American Association for Accreditation of Laboratory Animal Care (AAALAC) and all animal experiments were conducted in accordance with relevant guidelines and regulations and based on protocol approved by NUS Institutional Animal Care and Use Committee (IACUC). All methods were conducted in accordance with ARRIVE guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"5080"}}