{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:02:20Z","timestamp":1792724540255,"version":"4.5.0"},"reference-count":51,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2011,11,29]],"date-time":"2011-11-29T00:00:00Z","timestamp":1322524800000},"content-version":"vor","delay-in-days":28,"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":[[2011,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Patients with kidney failure frequently require the formation of an arterio\u2010venous fistula (AVF) in which a vein is connected to an artery resulting in arterialization of the vein to allow adequate blood flow into an external \u2018artificial kidney\u2019. In most patients, neo\u2010intimal hyperplasia (NIH) ensues, causing narrowing and subsequent occlusion of the vein, leading to significant morbidity. The cellular events causing venous NIH may serve as ideal targets for molecular\u2010based therapies. However, therapeutic gene delivery into the vascular system is seriously impeded by problems related to the low efficacy and toxicity of targeted viral vector delivery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>To explore the feasibility of a plasmid\u2010based vascular gene delivery system, we established a rat AVF model that develops NIH. Plasmids encoding for reporter or therapeutic genes were delivered into the blood vessels at the time or after AVF formation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Intra\u2010luminal injection of plasmid into the AVF resulted in extensive and long\u2010term reporter gene expression at the venous limb mainly at the site of NIH formation. Transgene expression was confined to endothelial cells and myofibroblasts that migrate inwards from the adventitia and form the NIH lesion. There was no detrimental tissue reaction to plasmid delivery, contrasting with the severe inflammatory response observed after adenovirus infection. Intra\u2010vascular delivery of a plasmid carrying the endothelial nitric oxide synthase gene resulted in sustained production of nitric oxide, previously shown to mitigate NIH formation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings open the possibility of vascular transduction with naked DNA bearing therapeutic genes in areas prone to NIH to ameliorate vein graft pathologies using simple and clinically applicable vector delivery methods. Copyright \u00a9 2011 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.1615","type":"journal-article","created":{"date-parts":[[2011,10,17]],"date-time":"2011-10-17T07:18:13Z","timestamp":1318835893000},"page":"611-621","source":"Crossref","is-referenced-by-count":9,"title":["Efficient transgene expression from naked DNA delivered into an arterio\u2010venous fistula model for kidney dialysis"],"prefix":"10.1002","volume":"13","author":[{"given":"Anat S.","family":"Globerman","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Surgery Hadassah University Hospital  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malka","family":"Chaouat","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Surgery Hadassah University Hospital  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zippora","family":"Shlomai","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Surgery Hadassah University Hospital  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eithan","family":"Galun","sequence":"additional","affiliation":[{"name":"Goldyne Savad Institute of Gene Therapy Hadassah University Hospital  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evelyn","family":"Zeira","sequence":"additional","affiliation":[{"name":"Goldyne Savad Institute of Gene Therapy Hadassah University Hospital  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gideon","family":"Zamir","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Surgery Hadassah University Hospital  Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,11,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfg483"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1998.00122.x"},{"issue":"1","key":"e_1_2_6_4_1","first-page":"S1","article-title":"Excerpts from the United States Renal Data System 2004 annual data report: atlas of end\u2010stage renal disease in the United States","volume":"55","author":"Collins AJ","year":"2010","journal-title":"Am J Kidney Dis"},{"issue":"5","key":"e_1_2_6_5_1","first-page":"13","article-title":"United States Renal Data System (USRDS)","volume":"20","author":"Agodoa L","year":"2000","journal-title":"Nefrologia"},{"key":"e_1_2_6_6_1","first-page":"150","article-title":"Biology of arteriovenous fistula failure","volume":"20","author":"Roy\u2010Chaudhury P","year":"2007","journal-title":"J Nephrol"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.00360705"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.195.1.7892454"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.94.7.1655"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2005.00763.x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.95.12.2684"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5223(97)70115-6"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/18.2.378"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2002.kid551.x"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/ajkd.2002.29886"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2001.00956.x"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.RVI.0000217928.43396.35"},{"key":"e_1_2_6_18_1","first-page":"88","article-title":"Fistula first: an update for renal providers","volume":"18","author":"Beasley C","year":"2004","journal-title":"Nephrol News Issues"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0741-5214(03)00732-8"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.14.1.148"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2119055"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.83.6.2007"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115970"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.71.1.27"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2660(05)54001-X"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1089\/hum.1992.3.1-21"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64339-8"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.102.11.1315"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(96)00211-8"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.6.12.1381691"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1293"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.4.1137"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302882"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.13.1274"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8047883"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2007.07.019"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.77.3.445"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2007.06.007"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfn708"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1161\/hh2401.100844"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.17.3.417"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.12.1362"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.19.6.1393"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9150(95)90073-X"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1161\/hc1002.105228"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.98.13.1335"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1089\/10430349950017004"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.10.4407"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.20.6.1452"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.82.12.1253"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.1.108"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.602532"}],"container-title":["The Journal of Gene Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjgm.1615","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jgm.1615","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T23:18:04Z","timestamp":1695511084000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jgm.1615"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,11]]},"references-count":51,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2011,11]]}},"alternative-id":["10.1002\/jgm.1615"],"URL":"https:\/\/doi.org\/10.1002\/jgm.1615","archive":["Portico"],"relation":{},"ISSN":["1099-498X","1521-2254"],"issn-type":[{"value":"1099-498X","type":"print"},{"value":"1521-2254","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,11]]}}}