{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T21:11:39Z","timestamp":1781817099709,"version":"3.54.5"},"reference-count":36,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T00:00:00Z","timestamp":1682035200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82000539"],"award-info":[{"award-number":["82000539"]}],"id":[{"id":"10.13039\/501100001809","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":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The broad application of clustered regularly interspaced short palindromic repeat\u00a0(CRISPR)\/Cas9 genome editing tools is hindered by challenges in the efficient delivery of its two components into specific cells and intracytoplasmic release. Herein, a novel copolymer for delivery of Cas9\u2010mRNA\/ single\u2010guide RNA (Cas9\u2010mRNA\/sgRNA) in vitro and vivo, using carboxylesterase\u2010responsive cationic triadic copolymeric nanoparticles targeted proprotein convertase subtilisin\/kexin type 9 (PCSK9) for hyperlipidemia amelioration is reported. A dimethyl biguanide derivative is designed and synthesized to form cationic block, and copolymerization onto prepolymer with propyl methacrylate, to fabricate a triadic copolymer mPEG<jats:italic>\u2010b\u2010<\/jats:italic>P(Met\/n\u2010PMA). The copolymer can self\u2010assemble with Cas9\u2010mRNA\/sgRNA, indicating the excellent potential of nanoparticles to form a delivery carrier. This vehicle can efficiently release RNA in response to the hepatocytes carboxylesterase for genome editing. It was demonstrated that the mPEG<jats:italic>\u2010b\u2010<\/jats:italic>P(Met\/n\u2010PMA)\/Cas9 mRNA\/sgRNA nanoparticles effectively accumulated in hepatocytes, lead to the inhibition of PCSK9, and lowered the levels of Low\u2010density lipoprotein\u00a0cholesterol and total cholesterol in mouse serum down 20% of nontreatment. Interestingly, the nanoparticles even enable multiple functions in the regulation of blood glucose and weight. This study establishes a novel method to achieve complex CRISPR components stable loading, safe delivery, and fixed\u2010point release, which expand the application of CRISPR delivery systems.<\/jats:p>","DOI":"10.1002\/advs.202300502","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T07:51:54Z","timestamp":1682063514000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["CES1\u2010Triggered Liver\u2010Specific Cargo Release of CRISPR\/Cas9 Elements by Cationic Triadic Copolymeric Nanoparticles Targeting Gene Editing of PCSK9 for Hyperlipidemia Amelioration"],"prefix":"10.1002","volume":"10","author":[{"given":"Yunfei","family":"Zhao","sequence":"first","affiliation":[{"name":"Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing Pharmacodynamic Evaluation Engineering Technology Research Center, College of Pharmacy Chongqing Medical University  Chongqing 400016 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Li","sequence":"additional","affiliation":[{"name":"Centre for Lipid Research &amp; Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education) Institute for Viral Hepatitis Department of Infectious Diseases the Second Affiliated Hospital Chongqing Medical University  Chongqing 400016 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Wang","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing Pharmacodynamic Evaluation Engineering Technology Research Center, College of Pharmacy Chongqing Medical University  Chongqing 400016 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuelan","family":"Gan","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing Pharmacodynamic Evaluation Engineering Technology Research Center, College of Pharmacy Chongqing Medical University  Chongqing 400016 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianye","family":"Zheng","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing Pharmacodynamic Evaluation Engineering Technology Research Center, College of Pharmacy Chongqing Medical University  Chongqing 400016 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengyue","family":"Chen","sequence":"additional","affiliation":[{"name":"Centre for Lipid Research &amp; Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education) Institute for Viral Hepatitis Department of Infectious Diseases the Second Affiliated Hospital Chongqing Medical University  Chongqing 400016 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wei","sequence":"additional","affiliation":[{"name":"Centre for Lipid Research &amp; Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education) Institute for Viral Hepatitis Department of Infectious Diseases the Second Affiliated Hospital Chongqing Medical University  Chongqing 400016 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4327-4330","authenticated-orcid":false,"given":"Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing Pharmacodynamic Evaluation Engineering Technology Research Center, College of Pharmacy Chongqing Medical University  Chongqing 400016 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8391-4080","authenticated-orcid":false,"given":"Chao","family":"Yu","sequence":"additional","affiliation":[{"name":"Chongqing Key Laboratory for Pharmaceutical Metabolism Research, Chongqing Pharmacodynamic Evaluation Engineering Technology Research Center, College of Pharmacy Chongqing Medical University  Chongqing 400016 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,21]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2016.280"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-022-07442-w"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201610209"},{"key":"e_1_2_8_2_3","doi-asserted-by":"publisher","DOI":"10.7150\/thno.47007"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2022.02.009"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4005"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201903618"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2022.103948"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.673286"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpolymj.2019.03.009"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbin.11202"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.27109"},{"key":"e_1_2_8_8_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2021.08.061"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7BM01096F"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mabi.201800468"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.0c04471"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2015.05.050"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1BM00909E"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/adtp.201900206"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-062613-093128"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5b08948"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.201903277"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules13020412"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.21.173"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.2174\/092986609789071324"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2018.05.005"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/adma.202003523"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12645-018-0045-5"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.snb.2020.128798"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1039\/C9RA08150J"},{"key":"e_1_2_8_23_3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202001107"},{"key":"e_1_2_8_23_4","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119486"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.201601293"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsami.0c14405"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202100196"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202010099"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202300502","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T20:14:33Z","timestamp":1759781673000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202300502"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,21]]},"references-count":36,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1002\/advs.202300502"],"URL":"https:\/\/doi.org\/10.1002\/advs.202300502","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,21]]},"assertion":[{"value":"2023-02-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2300502"}}