{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:26:27Z","timestamp":1792700787441,"version":"4.5.0"},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,5,28]],"date-time":"2023-05-28T00:00:00Z","timestamp":1685232000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018688","name":"Korea Disease Control and Prevention Agency","doi-asserted-by":"publisher","award":["2021ER240300"],"award-info":[{"award-number":["2021ER240300"]}],"id":[{"id":"10.13039\/100018688","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003569","name":"Ministry of Food and Drug Safety","doi-asserted-by":"publisher","award":["22203MFDS405"],"award-info":[{"award-number":["22203MFDS405"]}],"id":[{"id":"10.13039\/501100003569","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["2018M3A9H3020844"],"award-info":[{"award-number":["2018M3A9H3020844"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["2020R1A2C2004364"],"award-info":[{"award-number":["2020R1A2C2004364"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["2022M3A9H1014125"],"award-info":[{"award-number":["2022M3A9H1014125"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["2022M3E5F1081328"],"award-info":[{"award-number":["2022M3E5F1081328"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aiche.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Bioengineering &amp;amp; Transla Med"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>mRNA\u2010based protein replacement therapy has received much attention as a novel intervention in clinical disease treatment. Lipid nanoparticles (LNPs) are widely used for their therapeutic potential to efficiently deliver mRNA. However, clinical translation has been hampered by the immunogenicity of LNPs that may aggravate underlying disease states. Here, we report a novel ionizable LNP with enhanced potency and safety. The piperazine\u2010based biodegradable ionizable lipid (244cis) was developed for LNP formulation and its level of protein expression and immunogenicity in the target tissue was evaluated. It was found that 244cis LNP enabled substantial expression of the target protein (human erythropoietin), while it minimally induced the secretion of monocyte chemoattractant protein 1 (MCP\u20101) as compared to other conventional LNPs. Selective lung targeting of 244cis LNP was further investigated in tdTomato transgenic mice with bleomycin\u2010induced pulmonary fibrosis (PF). The repeated administration of 244cis LNP with Cre recombinase mRNA achieved complete transfection of lung endothelial cells (~80%) and over 40% transfection of Sca\u20101\u2010positive fibroblasts. It was shown that 244cis LNP allows the repeated dose of mRNA without the loss of activity due to its low immunogenicity. Our results demonstrate that 244cis LNP has great potential for the treatment of chronic diseases in the lungs with improved potency and safety.<\/jats:p>","DOI":"10.1002\/btm2.10556","type":"journal-article","created":{"date-parts":[[2023,5,29]],"date-time":"2023-05-29T02:10:56Z","timestamp":1685326256000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Novel piperazine\u2010based ionizable lipid nanoparticles allow the repeated dose of mRNA to fibrotic lungs with improved potency and safety"],"prefix":"10.1002","volume":"8","author":[{"given":"Minjeong","family":"Kim","sequence":"first","affiliation":[{"name":"College of Pharmacy, Graduate School of Pharmaceutical Sciences Ewha Womans University  Seoul South Korea"},{"name":"Department of Biochemistry, Simmons Comprehensive Cancer Center The University of Texas Southwestern Medical Center  Dallas Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Jeong","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Graduate School of Pharmaceutical Sciences Ewha Womans University  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyeongseok","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Graduate School of Pharmaceutical Sciences Ewha Womans University  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeji","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Graduate School of Pharmaceutical Sciences Ewha Womans University  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeongeun","family":"Park","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Graduate School of Pharmaceutical Sciences Ewha Womans University  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyein","family":"Jung","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Graduate School of Pharmaceutical Sciences Ewha Womans University  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seongeun","family":"Im","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Graduate School of Pharmaceutical Sciences Ewha Womans University  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo\u2010Sung","family":"Yang","sequence":"additional","affiliation":[{"name":"ST Pharm Co. Ltd.  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyungjin","family":"Kim","sequence":"additional","affiliation":[{"name":"ST Pharm Co. Ltd.  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9478-8473","authenticated-orcid":false,"given":"Hyukjin","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Graduate School of Pharmaceutical Sciences Ewha Womans University  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4278"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/natrevmats.2017.56"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.02.012"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.nanolett.5b02497"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201203263"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1553"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1716153"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2018.03.010"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202013927"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41563-020-00886-0"},{"key":"e_1_2_9_12_1","first-page":"9","article-title":"Engineered ionizable lipid nanoparticles for targeted delivery of RNA therapeutics into different types of cells in the liver","volume":"7","author":"Kim M","year":"2021","journal-title":"Sci Adv"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2026131"},{"key":"e_1_2_9_14_1","first-page":"5","article-title":"Non\u2010immunotherapy application of LNP\u2010mRNA: maximizing efficacy and safety","volume":"9","author":"Vlatkovic I","year":"2021","journal-title":"Biomedicine"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01007-w"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/immunohorizons.1900029"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2022.03.046"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41565-020-0669-6"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2109256118"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2017.11.005"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-016-0211-7"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-018-1719-4"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.11.081"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26714-w"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2008.85"}],"container-title":["Bioengineering &amp; 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