{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T22:42:24Z","timestamp":1774564944334,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2000,11,1]],"date-time":"2000-11-01T00:00:00Z","timestamp":973036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002342","name":"Suomalainen Tiedeakatemia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002342","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004092","name":"Kuopion Yliopistollinen Sairaala","doi-asserted-by":"publisher","award":["5130"],"award-info":[{"award-number":["5130"]}],"id":[{"id":"10.13039\/501100004092","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":[[2000,11]]},"abstract":"<jats:p>\n                    Expression of transgene other than in the target tissue may cause side effects and safety problems in gene therapy. We analyzed biodistribution of transgene expression after intravascular and periadventitial gene delivery methods using the first generation nuclear\u2010targeted\n                    <jats:italic>lacZ<\/jats:italic>\n                    adenovirus. RT\u2010PCR and X\u2010Gal stainings were used to study transgene expression 14 days after the gene transfer. After intravascular catheter\u2010mediated gene transfer to rabbit aorta mimicking angioplasty procedure, the target vessel showed 1.1% \u00b1 0.5 gene transfer efficiency. Other tissues showed varying\n                    <jats:italic>lacZ<\/jats:italic>\n                    gene expression indicating a systemic leakage of the vector with the highest transfection efficiency in hepatocytes (0.7% \u00b1 0.5). X\u2010Gal staining of blood cells 24 h after the intravascular gene transfer indicated that a significant portion (1.8% \u00b1 0.8) of circulating monocytes was transfected. X\u2010Gal\u2010positive cells were also found in testis. After periadventitial gene transfer using a closed silicon capsule placed around the artery, 0.1% \u00b1 0.1\n                    <jats:italic>lacZ<\/jats:italic>\n                    \u2010positive cells were detected in the artery wall. Positive cells were also found in the liver and testis (&lt;0.01%), indicating that the virus escapes even from the periadventitial space, although less extensively than during the intravascular application. We conclude that catheter\u2010mediated intravascular and, to a lesser extent, periadventitial gene transfer lead to leakage of adenovirus to systemic circulation, followed by expression of the transgene in several tissues. Possible consequences of the ectopic expression of the transgene should be evaluated in gene therapy trials even if local gene delivery methods are used.\u2014Hiltunen, M. O., Turunen, M. P., Turunen, A.\u2010M., Rissanen, T. T., Laitinen, M., Kosma, V.\u2010M., Yl\u00e4\u2010Herttuala, S. Biodistribution of adenoviral vector to nontarget tissues after local\n                    <jats:italic>in vivo<\/jats:italic>\n                    gene transfer to arterial wall using intravascular and periadventitial gene delivery methods.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    14, 2230\u20132236 (2000)\n                  <\/jats:p>","DOI":"10.1096\/fj.00-0145com","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T19:03:24Z","timestamp":1027710204000},"page":"2230-2236","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":76,"title":["Biodistribution of adenoviral vector to nontarget tissues after local\n                    <i>in vivo<\/i>\n                    gene transfer to arterial wall using intravascular and periadventitial gene delivery methods"],"prefix":"10.1096","volume":"14","author":[{"given":"Mikko O.","family":"Hiltunen","sequence":"first","affiliation":[{"name":"A. I. Virtanen Institute University of Kuopio Kuopio Finland"}]},{"given":"Mikko P.","family":"Turunen","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institute University of Kuopio Kuopio Finland"}]},{"given":"Anna\u2010Mari","family":"Turunen","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institute University of Kuopio Kuopio Finland"}]},{"given":"Tuomas T.","family":"Rissanen","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institute University of Kuopio Kuopio Finland"}]},{"given":"Marja","family":"Laitinen","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institute University of Kuopio Kuopio Finland"},{"name":"Department of Medicine University of Kuopio Kuopio Finland"}]},{"given":"Veli\u2010Matti","family":"Kosma","sequence":"additional","affiliation":[{"name":"Department of Pathology and Forensic medicine University of Kuopio Kuopio Finland"}]},{"given":"Seppo","family":"Yl\u00c4\u2010Herttuala","sequence":"additional","affiliation":[{"name":"A. I. Virtanen Institute University of Kuopio Kuopio Finland"},{"name":"Department of Medicine University of Kuopio Kuopio Finland"},{"name":"Gene Therapy Unit University of Kuopio Kuopio Finland"}]}],"member":"311","published-online":{"date-parts":[[2000,11]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(99)04180-X"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.1997.8.14-1645"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.1997.8.15-1737"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.1998.9.12-1769"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3300800"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2119055"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.90.4.1648"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.89.5.2190"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.1998.9.14-2135"},{"key":"e_1_2_6_11_1","first-page":"51","article-title":"Efficient catheter\u2010mediated gene transfer into the heart using replication\u2010defective adenovirus","volume":"1","author":"Barr E.","year":"1994","journal-title":"Gene Ther."},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.1998.9.10-1481"},{"key":"e_1_2_6_13_1","unstructured":"U. S. Pharmacopeia 2000 Chapter 1046 Cell and Gene Therapy Products"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1089\/10430340050015987"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117971"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4612-3900-0_5"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/43977"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.13.4.571"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(95)00635-4"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3300637"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.00-0145com","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.00-0145com","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.00-0145com","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T21:00:14Z","timestamp":1761685214000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.00-0145com"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,11]]},"references-count":19,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2000,11]]}},"alternative-id":["10.1096\/fj.00-0145com"],"URL":"https:\/\/doi.org\/10.1096\/fj.00-0145com","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,11]]},"assertion":[{"value":"2000-03-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-05-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-11-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}