{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:56:34Z","timestamp":1792205794945,"version":"4.4.0"},"reference-count":65,"publisher":"Wiley","issue":"31","license":[{"start":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T00:00:00Z","timestamp":1718668800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFC3404000"],"award-info":[{"award-number":["2023YFC3404000"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371781"],"award-info":[{"award-number":["82371781"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073752"],"award-info":[{"award-number":["82073752"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32070935"],"award-info":[{"award-number":["32070935"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013105","name":"Shanghai Rising-Star Program","doi-asserted-by":"publisher","award":["21QB1401800"],"award-info":[{"award-number":["21QB1401800"]}],"id":[{"id":"10.13039\/501100013105","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012543","name":"Shanghai Science and Technology Development Foundation","doi-asserted-by":"publisher","award":["20S11904700"],"award-info":[{"award-number":["20S11904700"]}],"id":[{"id":"10.13039\/100012543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Non\u2010alcoholic fatty liver disease (NAFLD) is a prominent cause of various chronic metabolic hepatic diseases with limited therapeutics. Rubicon, an essential regulator in lysosomal degradation, is reported to exacerbate hepatic steatosis in NAFLD mice and patients, indicating its probability of being a therapeutic target for NAFLD treatment. In this study, the therapeutic potential of Rubicon blockage is investigated. Lipid nanoparticles carrying Rubicon\u2010specific CRISPR\u2010Cas9 components exhibited liver accumulation, cell internalization, and Rubicon knockdown. A single administration of the nanoparticles results in attenuated lipid deposition and hepatic steatosis, with lower circulating lipid levels and decreased adipocyte size in NAFLD mice. Furthermore, the increase of phosphatidylcholine and phosphatidylethanolamine levels can be observed in the NAFLD mice livers after Rubicon silencing, along with regulatory effects on metabolism\u2010related genes such as CD36, Gpcpd1, Chka, and Lpin2. The results indicate that knockdown of Rubicon improves glycerophospholipid metabolism and thereby ameliorates the NAFLD progression, which provides a potential strategy for NAFLD therapy via the restoration of Rubicon.<\/jats:p>","DOI":"10.1002\/advs.202400493","type":"journal-article","created":{"date-parts":[[2024,6,19]],"date-time":"2024-06-19T01:50:33Z","timestamp":1718761833000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Lipid Nanoparticle\u2010Mediated Delivery of CRISPR\u2010Cas9 Against Rubicon Ameliorates NAFLD by Modulating CD36 Along with Glycerophospholipid Metabolism"],"prefix":"10.1002","volume":"11","author":[{"given":"Yu","family":"Bai","sequence":"first","affiliation":[{"name":"Department of Biological Medicines &amp; Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyang","family":"Nan","sequence":"additional","affiliation":[{"name":"Department of Biological Medicines &amp; Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biological Medicines &amp; Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Biological Medicines &amp; Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinlei","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Biological Medicines &amp; Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Research and Development Shanghai Proton and Heavy Ion Center Fudan University Cancer Hospital  Shanghai 201321 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Research and Development Shanghai Proton and Heavy Ion Center Fudan University Cancer Hospital  Shanghai 201321 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Dou","sequence":"additional","affiliation":[{"name":"Department of Biological Medicines &amp; Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaozhi","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Biological Medicines &amp; Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongrui","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Biological Medicines &amp; Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuwen","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Biological Medicines &amp; Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanzhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biological Medicines &amp; Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajun","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Biological Medicines &amp; Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy  Shanghai P. R. China"},{"name":"Fudan Zhangjiang Institute  Shanghai 201203 P. R. China"},{"name":"Shanghai Hailu Biological Technology Co., Ltd.  Shanghai 201200 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4305-9622","authenticated-orcid":false,"given":"Dianwen","family":"Ju","sequence":"additional","affiliation":[{"name":"Department of Biological Medicines &amp; Shanghai Engineering Research Center of Immunotherapeutics Fudan University School of Pharmacy  Shanghai P. R. China"},{"name":"Fudan Zhangjiang Institute  Shanghai 201203 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,18]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.01.052"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28524"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29724"},{"key":"e_1_2_9_4_1","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1136\/gutjnl-2023-331003","volume":"73","author":"Lee H.\u2010H.","year":"2024","journal-title":"Gut"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.08.023"},{"key":"e_1_2_9_6_1","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2023-075179","volume":"383","author":"Romero\u2010G\u00f3mez M.","year":"2023","journal-title":"BMJ"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24001"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvad095"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.04.015"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2020.101115"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-021-00502-9"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2018.06.031"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2021.11.009"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.10.015"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1846"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.9098"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abo5600"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17985-w"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2047341"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28820"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2021.09.016"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M090969"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202002273"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2020.1712107"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.EJ20-0326"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-018-0983-6"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2022.114416"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0BM01609H"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2023.114990"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.2c03234"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-020-0669-6"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.02.014"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abc9450"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1817426"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2020401118"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.09.040"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)33041-7"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00803-X"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.11.014"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2023.101238"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2023.101432"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21763"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep46658"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.03.007"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1408523111"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2023.08.031"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2023.2259732"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2023.2254191"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.01.011"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.601627"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.04.010"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/HEP.0000000000000375"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-021-01189-5"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-022-01689-y"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202301471"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2010.222844"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-27539-3"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41421-019-0091-0"},{"key":"e_1_2_9_59_1","volume":"168","author":"Bailey\u2010Hytholt C. M.","year":"2021","journal-title":"J. Vis. Exp."},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S366962"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-021-01032-w"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2020.1834711"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2018.04.022"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.845583"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-022-00710-w"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202400493","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T11:17:06Z","timestamp":1759749426000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202400493"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,18]]},"references-count":65,"journal-issue":{"issue":"31","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1002\/advs.202400493"],"URL":"https:\/\/doi.org\/10.1002\/advs.202400493","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,18]]},"assertion":[{"value":"2024-01-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2400493"}}