{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T04:55:09Z","timestamp":1761713709366,"version":"build-2065373602"},"reference-count":60,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2008,1,17]],"date-time":"2008-01-17T00:00:00Z","timestamp":1200528000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009153","name":"University of Portsmouth","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009153","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":[[2008,6]]},"abstract":"<jats:p>\n                    Poor nuclear entry, especially into nondividing cells, is a limiting factor in nonviral gene delivery. We have engineered a novel chimeric vector relying on the controlled assembly of a TAT\u2010tagged multisubunit DNA binding protein (\n                    <jats:italic>Eco<\/jats:italic>\n                    R124I) with expression plasmids containing the\n                    <jats:italic>Eco<\/jats:italic>\n                    R124I recognition site. Molecular interactions of this molecular assembly were studied by electrophoretic mobility shift assay and atomic force microscopy. Maintenance of nanocomplexes in an appropriate stoichiometric ratio was both necessary and sufficient to produce a signifi cant (&gt; 8\u2010fold) increase in the activity of the therapeutic a\u2010galactosidase A enzyme after intramuscular administration in the mouse model of Fabry disease. To our knowledge, this is the first molecular targeting system significantly enhancing plasmid\u2010based expression in skeletal muscle. Coinjection with pluronic SP1017 produced further enhancement of gene expression, demonstrating cumulative effects of the increased nuclear delivery by TAT chimeras and transcription activation by the pluronic. Cell penetration peptides (CPP), such as TAT, have been shown to improve delivery of macromolecules, when linked directly. However, in our system TAT\u2010enhanced targeting took place even though it was linked to the plasmid DNA molecule indirectly\n                    <jats:italic>via<\/jats:italic>\n                    two noncovalent bonds. Therefore, this proof\u2010of principle result indicates that TAT (and potentially other CPP) can be used for targeting modular chimeric vectors and therapeutic nanodevices.\u2014 Lavigne M. D., Yates, L., Coxhead, P., G\u00f3recki D. C. Nuclear\u2010targeted chimeric vector enhancing nonviral gene transfer into skeletal muscle of Fabry mice\n                    <jats:italic>in vivo<\/jats:italic>\n                    .\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    22, 2097\u20132107 (2008)\n                  <\/jats:p>","DOI":"10.1096\/fj.07-093765","type":"journal-article","created":{"date-parts":[[2008,1,17]],"date-time":"2008-01-17T20:45:21Z","timestamp":1200602721000},"page":"2097-2107","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Nuclear\u2010targeted chimeric vector enhancing nonviral gene transfer into skeletal muscle of Fabry mice\n                    <i>in vivo<\/i>"],"prefix":"10.1096","volume":"22","author":[{"given":"Matthieu D.","family":"Lavigne","sequence":"first","affiliation":[{"name":"School of Pharmacy and Biomedical Sciences University of Portsmouth Portsmouth UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Yates","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Biomedical Sciences University of Portsmouth Portsmouth UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Coxhead","sequence":"additional","affiliation":[{"name":"School of Biological Sciences Institute of Biomedical and Biomolecular Sciences University of Portsmouth Portsmouth UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dariusz C.","family":"G\u00f3recki","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Biomedical Sciences University of Portsmouth Portsmouth UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,1,17]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/156652306775515583"},{"key":"e_1_2_6_3_1","first-page":"191","article-title":"\u201cDressing\u2010up\u201d naked plasmids: Emerging nonviral gene therapy vectors","volume":"6","author":"G\u00f3recki D. 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