{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T02:17:16Z","timestamp":1791685036503,"version":"4.3.4"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"vor","delay-in-days":34,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100010256","name":"Guangzhou Municipal Science and Technology Project","doi-asserted-by":"publisher","award":["2023B03J1244"],"award-info":[{"award-number":["2023B03J1244"]}],"id":[{"id":"10.13039\/501100010256","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"DOI":"10.1038\/s41467-026-73544-9","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T15:46:10Z","timestamp":1784821570000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antioxidant malic-acid-derived lipid nanoparticles delivering secretory uricase circRNA for hyperuricemia and complication management in mice"],"prefix":"10.1038","volume":"17","author":[{"given":"Keqian","family":"Du","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawei","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijian","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shichao","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9341-4303","authenticated-orcid":false,"given":"Zhiming","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianlin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7579-2987","authenticated-orcid":false,"given":"Lin-Ping","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"73544_CR1","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1038\/s41392-024-01916-y","volume":"9","author":"L Du","year":"2024","unstructured":"Du, L. et al. Hyperuricemia and its related diseases: mechanisms and advances in therapy. Signal Transduct. Target Ther. 9, 212 (2024).","journal-title":"Signal Transduct. Target Ther."},{"key":"73544_CR2","doi-asserted-by":"publisher","DOI":"10.1186\/s12889-024-20799-w","volume":"24","author":"Y Li","year":"2024","unstructured":"Li, Y. et al. Global, regional, and national burden of gout in elderly 1990\u20132021: an analysis for the global burden of disease study 2021. BMC Public Health 24, 3298 (2024).","journal-title":"BMC Public Health"},{"key":"73544_CR3","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1038\/s41584-025-01228-7","volume":"21","author":"B G\u00e9rard","year":"2025","unstructured":"G\u00e9rard, B. et al. Hyperuricaemia and gout in the Pacific. Nat. Rev. Rheumatol. 21, 197\u2013210 (2025).","journal-title":"Nat. Rev. Rheumatol."},{"key":"73544_CR4","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1136\/annrheumdis-2012-201687","volume":"71","author":"M Doherty","year":"2012","unstructured":"Doherty, M. et al. Gout: why is this curable disease so seldom cured? Ann. Rheum. Dis. 71, 1765\u20131770 (2012).","journal-title":"Ann. Rheum. Dis."},{"key":"73544_CR5","doi-asserted-by":"publisher","first-page":"312","DOI":"10.3899\/jrheum.210009","volume":"49","author":"R Te Kampe","year":"2022","unstructured":"Te Kampe, R. et al. Outcomes of care among patients with gout in europe: a cross-sectional survey. J. Rheumatol. 49, 312\u2013319 (2022).","journal-title":"J. Rheumatol."},{"key":"73544_CR6","doi-asserted-by":"publisher","first-page":"879","DOI":"10.1002\/art.41247","volume":"72","author":"JD FitzGerald","year":"2020","unstructured":"FitzGerald, J. D. et al. 2020 American College of rheumatology guideline for the management of gout. Arthritis Rheumatol. 72, 879\u2013895 (2020).","journal-title":"Arthritis Rheumatol."},{"key":"73544_CR7","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1038\/nrd3349","volume":"10","author":"N Schlesinger","year":"2011","unstructured":"Schlesinger, N., Yasothan, U. & Kirkpatrick, P. Pegloticase. Nat. Rev. Drug Discov. 10, 17\u201318 (2011).","journal-title":"Nat. Rev. Drug Discov."},{"key":"73544_CR8","doi-asserted-by":"publisher","first-page":"3763","DOI":"10.1073\/pnas.1320393111","volume":"111","author":"JT Kratzer","year":"2014","unstructured":"Kratzer, J. T. et al. Evolutionary history and metabolic insights of ancient mammalian uricases. Proc. Natl. Acad. Sci. USA. 111, 3763\u20133768 (2014).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"73544_CR9","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202304123","volume":"35","author":"R Chen","year":"2023","unstructured":"Chen, R. et al. M2 macrophage hybrid membrane-camouflaged targeted biomimetic nanosomes to reprogram inflammatory microenvironment for enhanced enzyme-thermo-immunotherapy. Adv. Mater. 35, e2304123 (2023).","journal-title":"Adv. Mater."},{"key":"73544_CR10","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202305126","volume":"11","author":"Z Li","year":"2024","unstructured":"Li, Z. et al. Synthetic biohybrids of red blood cells and cascaded-enzymes@ metal-organic frameworks for hyperuricemia treatment. Adv. Sci. (Weinh) 11, e2305126 (2024).","journal-title":"Adv. Sci. (Weinh)"},{"key":"73544_CR11","doi-asserted-by":"publisher","DOI":"10.1186\/ar4497","volume":"16","author":"PE Lipsky","year":"2014","unstructured":"Lipsky, P. E. et al. Pegloticase immunogenicity: the relationship between efficacy and antibody development in patients treated for refractory chronic gout. Arthritis Res. Ther. 16, R60 (2014).","journal-title":"Arthritis Res. Ther."},{"key":"73544_CR12","doi-asserted-by":"publisher","first-page":"3548","DOI":"10.1016\/j.celrep.2017.11.081","volume":"21","author":"D An","year":"2017","unstructured":"An, D. et al. Systemic messenger RNA therapy as a treatment for methylmalonic acidemia. Cell Rep. 21, 3548\u20133558 (2017).","journal-title":"Cell Rep."},{"key":"73544_CR13","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47460-9","volume":"15","author":"R Baek","year":"2024","unstructured":"Baek, R. et al. Characterizing the mechanism of action for mRNA therapeutics for the treatment of propionic acidemia, methylmalonic acidemia, and phenylketonuria. Nat. Commun. 15, 3804 (2024).","journal-title":"Nat. Commun."},{"key":"73544_CR14","doi-asserted-by":"publisher","first-page":"165057","DOI":"10.1016\/j.cej.2025.165057","volume":"519","author":"K Du","year":"2025","unstructured":"Du, K. et al. Macrophage-targeted lipid nanoparticles based on Dendron-like lipids deliver mTOR inhibitor to alleviate systemic lupus erythematosus. Chem. Eng. J. 519, 165057 (2025).","journal-title":"Chem. Eng. J."},{"key":"73544_CR15","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":"73544_CR16","doi-asserted-by":"publisher","first-page":"2109","DOI":"10.1016\/j.ymthe.2022.04.011","volume":"30","author":"SM Moghimi","year":"2022","unstructured":"Moghimi, S. M. & Simberg, D. Pro-inflammatory concerns with lipid nanoparticles. Mol. Ther. 30, 2109\u20132110 (2022).","journal-title":"Mol. Ther."},{"key":"73544_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24960-6","volume":"12","author":"L-P Wu","year":"2021","unstructured":"Wu, L.-P. et al. Dendrimer end-terminal motif-dependent evasion of human complement and complement activation through IgM hitchhiking. Nat. Commun. 12, 4858 (2021).","journal-title":"Nat. Commun."},{"key":"73544_CR18","doi-asserted-by":"publisher","DOI":"10.1016\/j.biortech.2023.129629","volume":"387","author":"Y Chen","year":"2023","unstructured":"Chen, Y. et al. Engineering the metabolism and morphology of the filamentous fungus Trichoderma reesei for efficient L-malic acid production. Bioresour. Technol. 387, 129629 (2023).","journal-title":"Bioresour. Technol."},{"key":"73544_CR19","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-022-01497-4","volume":"20","author":"X Huang","year":"2022","unstructured":"Huang, X., Xu, L., Qian, H., Wang, X. & Tao, Z. Polymalic acid for translational nanomedicine. J. Nanobiotechnol. 20, 295 (2022).","journal-title":"J. Nanobiotechnol."},{"key":"73544_CR20","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42502-0","volume":"14","author":"F-L Zhang","year":"2023","unstructured":"Zhang, F.-L. et al. Organoids transplantation attenuates intestinal ischemia\/reperfusion injury in mice through L-Malic acid-mediated M2 macrophage polarization. Nat. Commun. 14, 6779 (2023).","journal-title":"Nat. Commun."},{"key":"73544_CR21","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.113653","volume":"144","author":"Z Ji","year":"2025","unstructured":"Ji, Z. et al. The malic acid inhibiting inflammation in ankylosing spondylitis by interfering M1 macrophage polarization. Int. Immunopharmacol. 144, 113653 (2025).","journal-title":"Int. Immunopharmacol."},{"key":"73544_CR22","doi-asserted-by":"publisher","first-page":"3014","DOI":"10.3390\/foods11193014","volume":"11","author":"Y Wang","year":"2022","unstructured":"Wang, Y. et al. Protective effects of several common amino acids, vitamins, organic acids, flavonoids and phenolic acids against hepatocyte damage caused by alcohol. Foods 11, 3014 (2022).","journal-title":"Foods"},{"key":"73544_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102889","volume":"67","author":"P Zhang","year":"2023","unstructured":"Zhang, P. et al. Maternal consumption of l-malic acid enriched diets improves antioxidant capacity and glucose metabolism in offspring by regulating the gut microbiota. Redox Biol. 67, 102889 (2023).","journal-title":"Redox Biol."},{"key":"73544_CR24","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1089\/end.2013.0477","volume":"28","author":"AL Rodgers","year":"2014","unstructured":"Rodgers, A. L., Webber, D., de Charmoy, R., Jackson, G. E. & Ravenscroft, N. Malic acid supplementation increases urinary citrate excretion and urinary pH: implications for the potential treatment of calcium oxalate stone disease. J. Endourol. 28, 229\u2013236 (2014).","journal-title":"J. Endourol."},{"key":"73544_CR25","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1136\/annrheumdis-2016-209707","volume":"76","author":"P Richette","year":"2017","unstructured":"Richette, P. et al. 2016 updated EULAR evidence-based recommendations for the management of gout. Ann. Rheum. Dis. 76, 29\u201342 (2017).","journal-title":"Ann. Rheum. Dis."},{"key":"73544_CR26","doi-asserted-by":"publisher","first-page":"1728","DOI":"10.1016\/j.cell.2022.03.044","volume":"185","author":"L Qu","year":"2022","unstructured":"Qu, L. et al. Circular RNA vaccines against SARS-CoV-2 and emerging variants. Cell 185, 1728\u20131744.e16 (2022).","journal-title":"Cell"},{"key":"73544_CR27","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-53242-0","volume":"15","author":"X Liu","year":"2024","unstructured":"Liu, X. et al. A single-dose circular RNA vaccine prevents Zika virus infection without enhancing dengue severity in mice. Nat. Commun. 15, 8932 (2024).","journal-title":"Nat. Commun."},{"key":"73544_CR28","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1093\/nar\/gkv1367","volume":"44","author":"Y Enuka","year":"2016","unstructured":"Enuka, Y. et al. Circular RNAs are long-lived and display only minimal early alterations in response to a growth factor. Nucleic Acids Res. 44, 1370\u20131383 (2016).","journal-title":"Nucleic Acids Res."},{"key":"73544_CR29","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1016\/j.molcel.2021.11.019","volume":"82","author":"C-X Liu","year":"2022","unstructured":"Liu, C.-X. et al. RNA circles with minimized immunogenicity as potent PKR inhibitors. Mol. Cell 82, 420\u2013434.e6 (2022).","journal-title":"Mol. Cell"},{"key":"73544_CR30","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.908517","volume":"13","author":"S Wang","year":"2022","unstructured":"Wang, S. et al. Research progress of risk factors and early diagnostic biomarkers of gout-induced renal injury. Front. Immunol. 13, 908517 (2022).","journal-title":"Front. Immunol."},{"key":"73544_CR31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejim.2020.07.006","volume":"80","author":"C Borghi","year":"2020","unstructured":"Borghi, C. et al. Hyperuricaemia and gout in cardiovascular, metabolic and kidney disease. Eur. J. Int. Med. 80, 1\u201311 (2020).","journal-title":"Eur. J. Int. Med."},{"key":"73544_CR32","doi-asserted-by":"publisher","first-page":"2158","DOI":"10.7150\/thno.40650","volume":"10","author":"A Mariotte","year":"2020","unstructured":"Mariotte, A. et al. A mouse model of MSU-induced acute inflammation in vivo suggests imiquimod-dependent targeting of Il-1\u03b2 as relevant therapy for gout patients. Theranostics 10, 2158 (2020).","journal-title":"Theranostics"},{"key":"73544_CR33","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":"73544_CR34","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1002\/jbm.a.37705","volume":"112","author":"K Mrksich","year":"2024","unstructured":"Mrksich, K. et al. Influence of ionizable lipid tail length on lipid nanoparticle delivery of mRNA of varying length. J. Biomed. Mater. Res. A 112, 1494\u20131505 (2024).","journal-title":"J. Biomed. Mater. Res. A"},{"key":"73544_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2023.122158","volume":"299","author":"Y Qin","year":"2023","unstructured":"Qin, Y. et al. Evaluation of a DoE based approach for comprehensive modelling of the effect of lipid nanoparticle composition on nucleic acid delivery. Biomaterials 299, 122158 (2023).","journal-title":"Biomaterials"},{"key":"73544_CR36","doi-asserted-by":"crossref","unstructured":"Miller, S. G. et al. Uric acid formation is driven by crosstalk between skeletal muscle and other cell types. JCI Insight 9, e171815 (2024).","DOI":"10.1172\/jci.insight.171815"},{"key":"73544_CR37","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s40104-025-01163-3","volume":"16","author":"H Jiang","year":"2025","unstructured":"Jiang, H. et al. Malic enzyme 3 mediated the effects of malic acid on intestinal redox status and feed efficiency in broilers. J. Anim. Sci. Biotechnol. 16, 28 (2025).","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"73544_CR38","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1080\/08923973.2019.1680688","volume":"41","author":"B Lee","year":"2019","unstructured":"Lee, B. et al. dl-Malic acid as a component of \u03b1-hydroxy acids: effect on 2,4-dinitrochlorobenzene-induced inflammation in atopic dermatitis-like skin lesions in vitro and in vivo. Immunopharmacol. Immunotoxicol. 41, 614\u2013621 (2019).","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"73544_CR39","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1038\/s41392-024-02076-9","volume":"9","author":"Y-J-N Chen","year":"2024","unstructured":"Chen, Y.-J. -N. et al. Malate initiates a proton-sensing pathway essential for pH regulation of inflammation. Signal Transduct. Target Ther. 9, 367 (2024).","journal-title":"Signal Transduct. Target Ther."},{"key":"73544_CR40","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1038\/s41396-018-0333-4","volume":"13","author":"P-H Wang","year":"2019","unstructured":"Wang, P.-H. et al. An interspecies malate\u2013pyruvate shuttle reconciles redox imbalance in an anaerobic microbial community. ISME J. 13, 1042\u20131055 (2019).","journal-title":"ISME J."},{"key":"73544_CR41","doi-asserted-by":"publisher","first-page":"a040550","DOI":"10.1101\/cshperspect.a040550","volume":"13","author":"NS Chandel","year":"2021","unstructured":"Chandel, N. S. NADPH\u2014the forgotten reducing equivalent. Cold Spring Harb. Perspect. Biol. 13, a040550 (2021).","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"73544_CR42","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-64734-y","volume":"16","author":"B Wang","year":"2025","unstructured":"Wang, B. et al. The integral membrane protein smim4 modulates redox balance via malate compartmentalization in pancreatic cancer. Nat. Commun. 16, 9772 (2025).","journal-title":"Nat. Commun."},{"key":"73544_CR43","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2313009120","volume":"120","author":"Q Cheng","year":"2023","unstructured":"Cheng, Q. et al. In situ production and secretion of proteins endow therapeutic benefit against psoriasiform dermatitis and melanoma. Proc. Natl. Acad. Sci. USA. 120, e2313009120 (2023).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"73544_CR44","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1016\/j.jbiotec.2006.11.026","volume":"128","author":"S Knappskog","year":"2007","unstructured":"Knappskog, S. et al. The level of synthesis and secretion of Gaussia princeps luciferase in transfected CHO cells is heavily dependent on the choice of signal peptide. J. Biotechnol. 128, 705\u2013715 (2007).","journal-title":"J. Biotechnol."},{"key":"73544_CR45","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2023.167009","volume":"1870","author":"L Pang","year":"2024","unstructured":"Pang, L. et al. A stable liver-specific urate oxidase gene knockout hyperuricemia mouse model finds activated hepatic de novo purine biosynthesis and urate nephropathy. Biochim. Biophys. Acta Mol. Basis Dis. 1870, 167009 (2024).","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"73544_CR46","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.kint.2017.04.031","volume":"93","author":"J Lu","year":"2018","unstructured":"Lu, J. et al. Knockout of the urate oxidase gene provides a stable mouse model of hyperuricemia associated with metabolic disorders. Kidney Int. 93, 69\u201380 (2018).","journal-title":"Kidney Int."},{"key":"73544_CR47","doi-asserted-by":"publisher","first-page":"2299","DOI":"10.1042\/CS20180563","volume":"132","author":"J Bao","year":"2018","unstructured":"Bao, J. et al. Pharmacological inhibition of autophagy by 3-MA attenuates hyperuricemic nephropathy. Clin. Sci. (Lond) 132, 2299\u20132322 (2018).","journal-title":"Clin. Sci. (Lond)"},{"key":"73544_CR48","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.coviro.2021.03.008","volume":"48","author":"BZ Igy\u00e1rt\u00f3","year":"2021","unstructured":"Igy\u00e1rt\u00f3, B. Z., Jacobsen, S. & Ndeupen, S. Future considerations for the mRNA-lipid nanoparticle vaccine platform. Curr. Opin. Virol. 48, 65\u201372 (2021).","journal-title":"Curr. Opin. Virol."},{"key":"73544_CR49","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.tibs.2020.09.008","volume":"46","author":"J Zhang","year":"2021","unstructured":"Zhang, J., Chen, D., Liang, G., Xu, W. & Tao, Z. Biosynthetic polymalic acid as a delivery nanoplatform for translational cancer medicine. Trends Biochem. Sci. 46, 213\u2013224 (2021).","journal-title":"Trends Biochem. Sci."},{"key":"73544_CR50","doi-asserted-by":"publisher","first-page":"18150","DOI":"10.1021\/acsami.5c00920","volume":"17","author":"J Lee","year":"2025","unstructured":"Lee, J. et al. Chirality-controlled lipid nanoparticles for mRNA delivery. ACS Appl. Mater. Interfaces 17, 18150\u201318159 (2025).","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"73544_CR51","doi-asserted-by":"publisher","first-page":"108615","DOI":"10.1016\/j.pharmthera.2024.108615","volume":"256","author":"S Wen","year":"2024","unstructured":"Wen, S., Arakawa, H. & Tamai, I. Uric acid in health and disease: from physiological functions to pathogenic mechanisms. Pharmacol. Ther. 256, 108615 (2024).","journal-title":"Pharmacol. Ther."},{"key":"73544_CR52","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1016\/j.jare.2017.03.003","volume":"8","author":"R El Ridi","year":"2017","unstructured":"El Ridi, R. & Tallima, H. Physiological functions and pathogenic potential of uric acid: a review. J. Adv. Res. 8, 487\u2013493 (2017).","journal-title":"J. Adv. Res."},{"key":"73544_CR53","doi-asserted-by":"publisher","DOI":"10.1186\/s12284-024-00729-5","volume":"17","author":"B Li","year":"2024","unstructured":"Li, B. et al. NADP-malic enzyme OsNADP-ME2 modulates plant height involving in gibberellin signaling in rice. Rice 17, 52 (2024).","journal-title":"Rice"},{"key":"73544_CR54","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202205436","volume":"10","author":"X Fang","year":"2023","unstructured":"Fang, X. et al. Malic Enzyme 1 as a novel anti-ferroptotic regulator in hepatic ischemia\/reperfusion injury. Adv. Sci. (Weinh) 10, e2205436 (2023).","journal-title":"Adv. Sci. (Weinh)"},{"key":"73544_CR55","doi-asserted-by":"publisher","first-page":"34449","DOI":"10.1021\/jacs.5c08376","volume":"147","author":"C Wang","year":"2025","unstructured":"Wang, C. et al. Strain-promoted mRNA transdermal delivery by lipoic lipid nanoparticles for therapeutic skin genome editing. J. Am. Chem. Soc. 147, 34449\u201334465 (2025).","journal-title":"J. Am. Chem. Soc."},{"key":"73544_CR56","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202407398","volume":"63","author":"M Cheng","year":"2024","unstructured":"Cheng, M. et al. Development of organ targeting lipid nanoparticles with low immunogenicity and their application in the treatment of pulmonary fibrosis. Angew. Chem. Int. Ed. Engl. 63, e202407398 (2024).","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"73544_CR57","doi-asserted-by":"publisher","first-page":"1852","DOI":"10.1038\/s41563-025-02240-8","volume":"24","author":"S Luozhong","year":"2025","unstructured":"Luozhong, S. et al. Poly(carboxybetaine) lipids enhance mRNA therapeutics efficacy and reduce their immunogenicity. Nat. Mater. 24, 1852\u20131861 (2025).","journal-title":"Nat. Mater."},{"key":"73544_CR58","doi-asserted-by":"publisher","first-page":"2181","DOI":"10.1038\/s41551-025-01422-8","volume":"9","author":"N Gong","year":"2025","unstructured":"Gong, N. et al. Mannich reaction-based combinatorial libraries identify antioxidant ionizable lipids for mRNA delivery with reduced immunogenicity. Nat. Biomed. Eng. 9, 2181\u20132195 (2025).","journal-title":"Nat. Biomed. Eng."},{"key":"73544_CR59","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-50752-9","volume":"15","author":"M Zhang","year":"2024","unstructured":"Zhang, M. et al. Atavistic strategy for the treatment of hyperuricemia via ionizable liposomal mRNA. Nat. Commun. 15, 6463 (2024).","journal-title":"Nat. Commun."},{"key":"73544_CR60","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1038\/s41584-023-01006-3","volume":"19","author":"N Schlesinger","year":"2023","unstructured":"Schlesinger, N., P\u00e9rez-Ruiz, F. & Liot\u00e9, F. Mechanisms and rationale for uricase use in patients with gout. Nat. Rev. Rheumatol. 19, 640\u2013649 (2023).","journal-title":"Nat. Rev. Rheumatol."},{"key":"73544_CR61","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202103672","volume":"9","author":"I Ozer","year":"2022","unstructured":"Ozer, I. et al. Polyethylene glycol-like brush polymer conjugate of a protein drug does not induce an antipolymer immune response and has enhanced pharmacokinetics than its polyethylene glycol counterpart. Adv. Sci. (Weinh) 9, e2103672 (2022).","journal-title":"Adv. Sci. (Weinh)"},{"key":"73544_CR62","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202310492","volume":"36","author":"Y Tang","year":"2024","unstructured":"Tang, Y., Du, Y., Ye, J., Deng, L. & Cui, W. Intestine-targeted explosive hydrogel microsphere promotes uric acid excretion for gout therapy. Adv. Mater. 36, e2310492 (2024).","journal-title":"Adv. Mater."},{"key":"73544_CR63","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1016\/j.jconrel.2024.06.042","volume":"372","author":"Z Ban","year":"2024","unstructured":"Ban, Z. et al. Immunogenicity-masking delivery of uricase against hyperuricemia and gout. J. Control Release 372, 862\u2013873 (2024).","journal-title":"J. Control Release"},{"key":"73544_CR64","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.1021\/acs.biomac.2c01388","volume":"24","author":"L Tran","year":"2023","unstructured":"Tran, L., Das, S., Zhao, L., Finn, M. G. & Gaucher, E. A. Oral delivery of nanoparticles carrying ancestral uricase enzyme protects against hyperuricemia in knockout mice. Biomacro 24, 2003\u20132008 (2023).","journal-title":"Biomacro"},{"key":"73544_CR65","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05096-6","volume":"9","author":"RA Wesselhoeft","year":"2018","unstructured":"Wesselhoeft, R. A., Kowalski, P. S. & Anderson, D. G. Engineering circular RNA for potent and stable translation in eukaryotic cells. Nat. Commun. 9, 2629 (2018).","journal-title":"Nat. Commun."},{"key":"73544_CR66","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1002\/hep.30252","volume":"69","author":"ME Inzaugarat","year":"2019","unstructured":"Inzaugarat, M. E. et al. NLR family pyrin domain-containing 3 inflammasome activation in hepatic stellate cells induces liver fibrosis in mice. Hepatology 69, 845\u2013859 (2019).","journal-title":"Hepatology"},{"key":"73544_CR67","doi-asserted-by":"publisher","DOI":"10.1002\/smll.202308749","volume":"20","author":"C Chen","year":"2024","unstructured":"Chen, C. et al. Monosodium urate crystal-induced pyroptotic cell death in neutrophil and macrophage facilitates the pathological progress of gout. Small 20, e2308749 (2024).","journal-title":"Small"}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-73544-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-73544-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-73544-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T11:03:45Z","timestamp":1787742225000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-026-73544-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,23]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["73544"],"URL":"https:\/\/doi.org\/10.1038\/s41467-026-73544-9","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,23]]},"assertion":[{"value":"2 December 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Nanjing AuroRNA Biotechnology Co.,LTD have filed a patent application related to malic acid-derived lipids for LNP formulation in this study. S.S and D.H serves as employers for Nanjing AuroRNA Biotechnology Co.,LTD. Other authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"8997"}}