{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:31:21Z","timestamp":1789605081614,"version":"build-2803163510"},"reference-count":45,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100004480","name":"Shanxi Province Natural Science Foundation","doi-asserted-by":"publisher","award":["201901D111210"],"award-info":[{"award-number":["201901D111210"]}],"id":[{"id":"10.13039\/501100004480","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004480","name":"Shanxi Province Natural Science Foundation","doi-asserted-by":"publisher","award":["202203021221186"],"award-info":[{"award-number":["202203021221186"]}],"id":[{"id":"10.13039\/501100004480","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Controlled Release"],"published-print":{"date-parts":[[2026,9]]},"DOI":"10.1016\/j.jconrel.2026.115117","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T15:36:28Z","timestamp":1781969788000},"page":"115117","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Preclinical efficacy of engineered CircRNA-GDF15@LNP for sustained weight loss and metabolic regulation in diet-induced obese mice"],"prefix":"10.1016","volume":"397","author":[{"given":"Weiyan","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanli","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thumb Tai","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunxia","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulei","family":"Qian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sicen","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"She","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Bian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"10481","key":"10.1016\/j.jconrel.2026.115117_bb0005","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/S0140-6736(25)00397-6","article-title":"Global, regional, and national prevalence of child and adolescent overweight and obesity, 1990–2021, with forecasts to 2050: a forecasting study for the Global Burden of Disease Study 2021","volume":"405","author":"Kerr","year":"2025","journal-title":"Lancet"},{"issue":"10481","key":"10.1016\/j.jconrel.2026.115117_bb0010","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/S0140-6736(25)00355-1","article-title":"Global, regional, and national prevalence of adult overweight and obesity, 1990–2021, with forecasts to 2050: a forecasting study for the Global Burden of Disease Study 2021","volume":"405","author":"Ng","year":"2025","journal-title":"Lancet"},{"issue":"10456","key":"10.1016\/j.jconrel.2026.115117_bb0015","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1016\/S0140-6736(24)01210-8","article-title":"Obesity in adults","volume":"404","author":"Lingvay","year":"2024","journal-title":"Lancet"},{"key":"10.1016\/j.jconrel.2026.115117_bb0020","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2022.879617","article-title":"Frontiers in metabolic physiology grand challenges","volume":"13","author":"Imig","year":"2022","journal-title":"Front. Physiol."},{"issue":"7","key":"10.1016\/j.jconrel.2026.115117_bb0025","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1016\/j.clnu.2024.05.035","article-title":"Reductions of food intake and body weight in diet-induced obese rats following chronic treatment with a monomeric peptide multiagonist","volume":"43","author":"Elfers","year":"2024","journal-title":"Clin. Nutr."},{"issue":"5","key":"10.1016\/j.jconrel.2026.115117_bb0030","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.soard.2020.01.015","article-title":"The incidence and determinants of bariatric reoperations: a population-based cohort study","volume":"16","author":"Morgan","year":"2020","journal-title":"Surg. Obes. Relat. Dis."},{"issue":"7968","key":"10.1016\/j.jconrel.2026.115117_bb0035","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1038\/s41586-023-06249-4","article-title":"GDF15 promotes weight loss by enhancing energy expenditure in muscle","volume":"619","author":"Wang","year":"2023","journal-title":"Nature"},{"issue":"30","key":"10.1016\/j.jconrel.2026.115117_bb0040","doi-asserted-by":"crossref","first-page":"2387","DOI":"10.2174\/0113816128318741240611114448","article-title":"Comprehensive role of GDF15 in inhibiting Adipogenesis and hyperlipidemia, enhancing cardiovascular health and alleviating inflammation in metabolic disorders","volume":"30","author":"Nayak","year":"2024","journal-title":"Curr. Pharm. Des."},{"issue":"2","key":"10.1016\/j.jconrel.2026.115117_bb0045","doi-asserted-by":"crossref","DOI":"10.1210\/jendso\/bvaf013","article-title":"Effects of acute exercise and carbohydrate intake on plasma GDF-15 levels and its association with appetite regulation","volume":"9","author":"James","year":"2025","journal-title":"J. Endocr. Soc."},{"issue":"10","key":"10.1016\/j.jconrel.2026.115117_bb0050","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1038\/nm.4392","article-title":"GFRAL is the receptor for GDF15 and the ligand promotes weight loss in mice and nonhuman primates","volume":"23","author":"Mullican","year":"2017","journal-title":"Nat. Med."},{"issue":"412","key":"10.1016\/j.jconrel.2026.115117_bb0055","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aan8732","article-title":"Long-acting MIC-1\/GDF15 molecules to treat obesity: evidence from mice to monkeys","volume":"9","author":"Xiong","year":"2017","journal-title":"Sci. Transl. Med."},{"issue":"1","key":"10.1016\/j.jconrel.2026.115117_bb0060","doi-asserted-by":"crossref","first-page":"8921","DOI":"10.1038\/s41598-021-87959-5","article-title":"Fc-GDF15 glyco-engineering and receptor binding affinity optimization for body weight regulation","volume":"11","author":"Fung","year":"2021","journal-title":"Sci. Rep."},{"issue":"2","key":"10.1016\/j.jconrel.2026.115117_bb0065","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.cmet.2022.12.011","article-title":"Discovery, development, and clinical proof of mechanism of LY3463251, a long-acting GDF15 receptor agonist","volume":"35","author":"Benichou","year":"2023","journal-title":"Cell Metab."},{"issue":"4","key":"10.1016\/j.jconrel.2026.115117_bb0070","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s44222-024-00259-1","article-title":"Engineering circular RNA medicines","volume":"3","author":"Cao","year":"2025","journal-title":"Nat. Rev. Bioeng."},{"issue":"7","key":"10.1016\/j.jconrel.2026.115117_bb0075","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1038\/s41587-024-02393-y","article-title":"Chemical and topological design of multicapped mRNA and capped circular RNA to augment translation","volume":"43","author":"Chen","year":"2025","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.jconrel.2026.115117_bb0080","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.omtn.2022.04.010","article-title":"Subcutaneous delivery of FGF21 mRNA therapy reverses obesity, insulin resistance, and hepatic steatosis in diet-induced obese mice","volume":"28","author":"Bartesaghi","year":"2022","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"10.1016\/j.jconrel.2026.115117_bb0085","doi-asserted-by":"crossref","DOI":"10.1016\/j.jconrel.2025.113857","article-title":"A combinatorial siRNA and mRNA approach for obesity treatment using targeting lipid nanoparticles","volume":"383","author":"Stewart","year":"2025","journal-title":"J. Control. Release"},{"key":"10.1016\/j.jconrel.2026.115117_bb0090","series-title":"Ribozyme self-splicing-based residual-sequence-free circular RNA and preparation method therefor. CN119040364B","author":"Dongsheng","year":"2024"},{"key":"10.1016\/j.jconrel.2026.115117_bb0095","series-title":"Circular RNAS and Preparation Methods Thereof. US12247202B2","author":"Dongsheng","year":"2025"},{"issue":"7868","key":"10.1016\/j.jconrel.2026.115117_bb0100","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/s41586-021-03653-6","article-title":"BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells in humans","volume":"595","author":"Sahin","year":"2021","journal-title":"Nature"},{"issue":"6","key":"10.1016\/j.jconrel.2026.115117_bb0105","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1016\/j.ymthe.2018.03.010","article-title":"A novel amino lipid series for mRNA delivery: improved endosomal escape and sustained pharmacology and safety in non-human Primates","volume":"26","author":"Sabnis","year":"2018","journal-title":"Mol. Ther."},{"issue":"39","key":"10.1016\/j.jconrel.2026.115117_bb0110","doi-asserted-by":"crossref","first-page":"2404510","DOI":"10.1002\/adfm.202404510","article-title":"Beyond the endosomal bottleneck: understanding the efficiency of mRNA\/LNP delivery","volume":"34","author":"Liu","year":"2024","journal-title":"Adv. Funct. Mater."},{"issue":"7","key":"10.1016\/j.jconrel.2026.115117_bb0115","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1124\/dmd.122.000980","article-title":"Biodistribution of lipid 5, mRNA, and its translated protein following intravenous administration of mRNA-encapsulated lipid nanoparticles in rats","volume":"51","author":"Ci","year":"2023","journal-title":"Drug Metab. Dispos."},{"issue":"11","key":"10.1016\/j.jconrel.2026.115117_bb0120","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.3390\/pharmaceutics12111095","article-title":"Manufacturing considerations for the development of lipid nanoparticles using microfluidics","volume":"12","author":"Roces","year":"2020","journal-title":"Pharmaceutics"},{"issue":"1","key":"10.1016\/j.jconrel.2026.115117_bb0125","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1038\/s41392-022-00996-y","article-title":"COVID-19 vaccine development: milestones, lessons and prospects","volume":"7","author":"Li","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"issue":"23","key":"10.1016\/j.jconrel.2026.115117_bb0130","doi-asserted-by":"crossref","first-page":"6284","DOI":"10.1158\/1078-0432.CCR-20-0472","article-title":"Intratumoral IL12 mRNA therapy promotes TH1 transformation of the tumor microenvironment","volume":"26","author":"Hewitt","year":"2020","journal-title":"Clin. Cancer Res."},{"issue":"7","key":"10.1016\/j.jconrel.2026.115117_bb0135","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1016\/j.ymthe.2024.04.036","article-title":"Development of an mRNA-based therapeutic vaccine mHTV-03E2 for high-risk HPV-related malignancies","volume":"32","author":"Wang","year":"2024","journal-title":"Mol. Ther. J. Am. Soc. Gene Ther."},{"issue":"6753","key":"10.1016\/j.jconrel.2026.115117_bb0140","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1126\/science.ads8473","article-title":"In vivo CAR T cell generation to treat cancer and autoimmune disease","volume":"388","author":"Hunter","year":"2025","journal-title":"Science"},{"issue":"6","key":"10.1016\/j.jconrel.2026.115117_bb0145","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1038\/s12276-024-01220-3","article-title":"Molecular mechanisms of circular RNA translation","volume":"56","author":"Hwang","year":"2024","journal-title":"Exp. Mol. Med."},{"issue":"9","key":"10.1016\/j.jconrel.2026.115117_bb0150","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1136\/gutjnl-2023-331742","article-title":"RNA-based therapies in liver metabolic diseases","volume":"74","author":"Fontanellas","year":"2025","journal-title":"Gut"},{"issue":"10","key":"10.1016\/j.jconrel.2026.115117_bb0155","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1038\/nm.4394","article-title":"GFRAL is the receptor for GDF15 and is required for the anti-obesity effects of the ligand","volume":"23","author":"Yang","year":"2017","journal-title":"Nat. Med."},{"issue":"21","key":"10.1016\/j.jconrel.2026.115117_bb0160","doi-asserted-by":"crossref","first-page":"11514","DOI":"10.1073\/pnas.94.21.11514","article-title":"MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-beta superfamily","volume":"94","author":"Bootcov","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"1","key":"10.1016\/j.jconrel.2026.115117_bb0165","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/jlb.65.1.2","article-title":"MIC-1 is a novel TGF-beta superfamily cytokine associated with macroph age activation","volume":"65","author":"Fairlie","year":"1999","journal-title":"J. Leukoc. Biol."},{"issue":"3","key":"10.1016\/j.jconrel.2026.115117_bb0170","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.jhep.2023.05.011","article-title":"Hepatic glucuronyl C5-epimerase combats obesity by stabilising GDF15","volume":"79","author":"He","year":"2023","journal-title":"J. Hepatol."},{"issue":"4","key":"10.1016\/j.jconrel.2026.115117_bb0175","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1038\/s41576-024-00806-x","article-title":"The therapeutic potential of circular RNAs","volume":"26","author":"O'Leary","year":"2025","journal-title":"Nat. Rev. Genet."},{"issue":"1","key":"10.1016\/j.jconrel.2026.115117_bb0180","doi-asserted-by":"crossref","first-page":"4383","DOI":"10.1038\/s41467-018-06318-7","article-title":"Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations","volume":"9","author":"MacParland","year":"2018","journal-title":"Nat. Commun."},{"issue":"1","key":"10.1016\/j.jconrel.2026.115117_bb0185","article-title":"Why do lipid nanoparticles target the liver? Understanding of biodistribution and liver-specific tropism. Molecular therapy","volume":"33","author":"Hosseini-Kharat","year":"2025","journal-title":"Meth. Clin. Develop."},{"key":"10.1016\/j.jconrel.2026.115117_bb0190","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.jconrel.2016.05.059","article-title":"Influence of particle size on the in vivo potency of lipid nanoparticle formulations of siRNA","volume":"235","author":"Chen","year":"2016","journal-title":"J. Control. Release"},{"issue":"9","key":"10.1016\/j.jconrel.2026.115117_bb0195","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.abf4398","article-title":"Engineered ionizable lipid nanoparticles for targeted delivery of RNA therapeutics into different types of cells in the liver","volume":"7","author":"Kim","year":"2021","journal-title":"Sci. Adv."},{"issue":"12","key":"10.1016\/j.jconrel.2026.115117_bb0200","doi-asserted-by":"crossref","DOI":"10.1016\/j.cmet.2023.11.003","article-title":"GDF15 is a major determinant of ketogenic diet-induced weight loss","volume":"35","author":"Lu","year":"2023","journal-title":"Cell Metab."},{"key":"10.1016\/j.jconrel.2026.115117_bb0205","doi-asserted-by":"crossref","DOI":"10.1016\/j.metabol.2023.155772","article-title":"GDF15 activates AMPK and inhibits gluconeogenesis and fibrosis in the liver by attenuating the TGF-\u03b21\/SMAD3 pathway","volume":"152","author":"Jurado-Aguilar","year":"2024","journal-title":"Metabolism"},{"issue":"1","key":"10.1016\/j.jconrel.2026.115117_bb0210","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.abb.2011.04.010","article-title":"AMPK activation enhances PPAR\u03b1 activity to inhibit cardiac hypertrophy via ERK1\/2 MAPK signaling pathway","volume":"511","author":"Meng","year":"2011","journal-title":"Arch. Biochem. Biophys."},{"issue":"3","key":"10.1016\/j.jconrel.2026.115117_bb0215","doi-asserted-by":"crossref","first-page":"718","DOI":"10.2337\/db08-1098","article-title":"Reduced adipose tissue oxygenation in human obesity: evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response","volume":"58","author":"Pasarica","year":"2009","journal-title":"Diabetes"},{"issue":"1","key":"10.1016\/j.jconrel.2026.115117_bb0220","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/S0303-7207(01)00394-X","article-title":"Chemokines control fat accumulation and leptin secretion by cultured human adipocytes","volume":"175","author":"Gerhardt","year":"2001","journal-title":"Mol. Cell. Endocrinol."},{"issue":"2","key":"10.1016\/j.jconrel.2026.115117_bb0225","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.cell.2009.12.052","article-title":"Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression","volume":"140","author":"Park","year":"2010","journal-title":"Cell"}],"container-title":["Journal of Controlled Release"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168365926005201?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0168365926005201?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T03:54:23Z","timestamp":1788666863000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0168365926005201"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":45,"alternative-id":["S0168365926005201"],"URL":"https:\/\/doi.org\/10.1016\/j.jconrel.2026.115117","relation":{},"ISSN":["0168-3659"],"issn-type":[{"value":"0168-3659","type":"print"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Preclinical efficacy of engineered CircRNA-GDF15@LNP for sustained weight loss and metabolic regulation in diet-induced obese mice","name":"articletitle","label":"Article Title"},{"value":"Journal of Controlled Release","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jconrel.2026.115117","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"115117"}}