{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T10:40:22Z","timestamp":1761561622798},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2012,4,17]],"date-time":"2012-04-17T00:00:00Z","timestamp":1334620800000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2012,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>A considerable percentage of tumors are not amenable to surgery. We have designed a simple and powerful targeting system that offers an alternative option for the multi\u2010component pre\u2010targeting strategies used clinically. This targeting system can be used for any type of solid tumors independent of the tumor type, thereby omitting the need to engineer unique antibodies for each specific application or tumour type. In the present study, we show the expression of a chimeric fusion protein, which contains the low\u2010density lipoprotein receptor transmembrane domains and avidin, after local gene transfer and its ability to bind biotinylated compounds <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Semliki Forest virus and lentivirus vectors were used to express the fusion protein with a high affinity binding site for biotinylated compounds in the tumor. Three different animal models and imaging modalities were used for the demonstration of the functionality and efficacy of the targeting system <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We demonstrate targeting of biotinylated compounds after local gene transfer <jats:italic>in vivo<\/jats:italic> using two different gene transfer vectors. The findings were confirmed by immunohistochemistry, single\u2010photon emission computed tomography and magnetic resonance imaging. The therapeutic efficacy was tested in a syngeneic rat glioma model by injecting biotinylated\u2010<jats:sup>90<\/jats:sup>Yttrium into the tail vein of glioma bearing rats. The study demonstrates that animals, which were treated by using the gene therapy based targeting system, lived significantly longer than control animals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our gene therapy based targeting system is a promising tool for the treatment of inoperable tumors and other disease conditions, as well as diagnostic imaging. Copyright \u00a9 2012 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.2619","type":"journal-article","created":{"date-parts":[[2012,3,12]],"date-time":"2012-03-12T14:34:08Z","timestamp":1331562848000},"page":"221-230","source":"Crossref","is-referenced-by-count":6,"title":["Efficient gene therapy based targeting system for the treatment of inoperable tumors"],"prefix":"10.1002","volume":"14","author":[{"given":"Thomas","family":"Wirth","sequence":"first","affiliation":[{"name":"AI Virtanen Institute University of Eastern Finland  Kuopio Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jere Tuomas","family":"Pikkarainen","sequence":"additional","affiliation":[{"name":"AI Virtanen Institute University of Eastern Finland  Kuopio Finland"},{"name":"Ark Therapeutics Oy  Kuopio Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haritha Dhammika","family":"Samaranayake","sequence":"additional","affiliation":[{"name":"AI Virtanen Institute University of Eastern Finland  Kuopio Finland"},{"name":"Ark Therapeutics Oy  Kuopio Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pauliina","family":"Lehtolainen\u2010Dalkilic","sequence":"additional","affiliation":[{"name":"Ark Therapeutics Oy  Kuopio Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna Pirita","family":"Lesch","sequence":"additional","affiliation":[{"name":"AI Virtanen Institute University of Eastern Finland  Kuopio Finland"},{"name":"Ark Therapeutics Oy  Kuopio Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kari Juhani","family":"Airenne","sequence":"additional","affiliation":[{"name":"AI Virtanen Institute University of Eastern Finland  Kuopio Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Varpu","family":"Marjom\u00e4ki","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Science University of Jyv\u00e4skyl\u00e4  Jyv\u00e4skyl\u00e4 Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seppo Pasi Antero","family":"Yl\u00e4\u2010Herttuala","sequence":"additional","affiliation":[{"name":"AI Virtanen Institute University of Eastern Finland  Kuopio Finland"},{"name":"Department of Medicine and Gene Therapy Unit University of Eastern Finland  Kuopio Finland"},{"name":"Gene Therapy Unit Kuopio University Hospital  Kuopio Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,4,17]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-007-0293-7"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(03)00014-7"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(09)70025-7"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/02688690802182256"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10143-006-0051-7"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-679X(08)60597-X"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2009.007"},{"key":"e_1_2_6_9_1","first-page":"259","article-title":"HIV\u2010based vectors. Preparation and use","volume":"69","author":"Follenzi A","year":"2002","journal-title":"Methods Mol Med"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.12.4284"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109431200"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-169X.1997.t01-5-00009.x"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.20834"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cgt.7700132"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-004-1488-y"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00259-002-1015-y"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1088\/0031-9155\/48\/13\/308"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002590050397"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.1153"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)01054-1"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0734-9750(01)00065-9"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6600047"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2388(199812)15:4<235::AID-SSU10>3.0.CO;2-B"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1179\/016164106X116782"},{"key":"e_1_2_6_25_1","first-page":"343","article-title":"Antibody\u2010dependent signal amplification in tumour xenografts after pretreatment with biotinylated monoclonal antibody and avidin or streptavidin","volume":"37","author":"Kassis AI","year":"1996","journal-title":"J Nucl Med"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-07-2384"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0103-129"}],"container-title":["The Journal of Gene Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjgm.2619","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jgm.2619","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T07:56:57Z","timestamp":1698652617000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jgm.2619"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,4]]},"references-count":26,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2012,4]]}},"alternative-id":["10.1002\/jgm.2619"],"URL":"https:\/\/doi.org\/10.1002\/jgm.2619","archive":["Portico"],"relation":{},"ISSN":["1099-498X","1521-2254"],"issn-type":[{"value":"1099-498X","type":"print"},{"value":"1521-2254","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,4]]}}}