{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T20:11:06Z","timestamp":1783109466848,"version":"3.54.6"},"reference-count":29,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2009,4,24]],"date-time":"2009-04-24T00:00:00Z","timestamp":1240531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["284205"],"award-info":[{"award-number":["284205"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2009,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Compartmentalization within eukaryotic cells hinders the efficient delivery of therapeutic agents to the cell nucleus. Here we describe novel multifunctional DNA carriers (MDCs) that self\u2010assemble with DNA to form structured nanoparticles that possess virus\u2010like functions for cellular trafficking. MDCs contain, in fusion, the DNA\u2010compacting sperm chromatin component protamine, \u03b1\u2010melanocyte\u2010stimulating hormone for cell\u2010targeted internalization, the endosometranslocation domain of diphtheria toxin, and an optimized nuclear localization sequence to confer recognition by the nuclear import machinery. The structure of the MDC\u2010DNA particles was examined using atomic force microscopy, and the functionality of each domain assessed using\n                    <jats:italic>in vitro<\/jats:italic>\n                    techniques, including a reconstituted nuclear transport assay in semi\u2010intact cells relying on the use of quantitative confocal laser scanning microscopy. The nanoparticles were internalized in cell\u2010specific fashion and subsequently exited the endosome into the cytoplasm. Notably, the nanoparticles interact with cellular nuclear transport proteins as shown in direct binding assays and are actively trafficked into the cell nucleus of nondividing cells, resulting in 3\u2010 to 4\u2010fold higher reporter gene expression in growth\u2010arrested human embryonic kidney cells, as well as lower cytotoxicity, than lipid and polyethyleneimine vectors. The importance of each functional domain was examined by comparing MDCs with different domain compositions as controls, as well as using antibodies to block particular pathways. MDCs that utilize cellular signaling pathways have enormous potential to safely and efficiently deliver therapeutic transgenes into the nucleus of nondividing cells.\u2014Glover, D. J., Ng, S. M., Mechler, A., Martin, L. L., Jans, D. A. Multifunctional protein nanocarriers for targeted nuclear gene delivery in nondividing cells.\n                    <jats:italic>FASEBJ.<\/jats:italic>\n                    23, 2996\u20133006 (2009).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.09-131425","type":"journal-article","created":{"date-parts":[[2009,4,24]],"date-time":"2009-04-24T20:44:37Z","timestamp":1240605877000},"page":"2996-3006","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Multifunctional protein nanocarriers for targeted nuclear gene delivery in nondividing cells"],"prefix":"10.1096","volume":"23","author":[{"given":"Dominic J.","family":"Glover","sequence":"first","affiliation":[{"name":"Nuclear Signalling Laboratory Department of Biochemistry and Molecular Biology Monash University Monash Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su May","family":"Ng","sequence":"additional","affiliation":[{"name":"Department of Chemistry Monash University Monash Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Mechler","sequence":"additional","affiliation":[{"name":"Department of Chemistry Monash University Monash Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisandra L.","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Chemistry Monash University Monash Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Jans","sequence":"additional","affiliation":[{"name":"Nuclear Signalling Laboratory Department of Biochemistry and Molecular Biology Monash University Monash Victoria Australia"},{"name":"ARC Centre of Excellence for Biotechnology and Development Canberra Australian Capital Territory Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,4,24]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1577"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1960"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/25.11.2221"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.286.5437.120"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02581"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nnano.2007.387"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2005.02.071"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600441"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2004.01.001"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi602381z"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.33.20328"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2004.11.031"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0888fje"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300093"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.27.17191"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2007.05712.x"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10895-005-2819-5"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.121067698"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20060466"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1046-5928(02)00610-1"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M312777200"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi048046i"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3300524"},{"key":"e_1_2_5_26_1","first-page":"845","article-title":"Which mechanism for nuclear import of plasmid DNA complexed with polyethylenimine derivatives?","volume":"8","author":"Grosse S.","year":"2006","journal-title":"J. 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