2015
DOI: 10.1089/hum.2014.084
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Efficient Gene Transfer and Durable Transgene Expression in Grafted Rabbit Veins

Abstract: Venous bypass grafts are useful treatments for obstructive coronary artery disease. However, their usefulness is limited by accelerated atherosclerosis. Genetic engineering of venous bypass grafts that prevented atherosclerosis could improve long-term graft patency and clinical outcomes. We used a rabbit model of jugular vein-to-carotid interposition grafting to develop gene therapy for vein-graft atherosclerosis. Rabbit veins were easily transduced in situ with a first-generation adenoviral vector; however, m… Show more

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Cited by 7 publications
(14 citation statements)
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“…We delayed transduction until 4 weeks after grafting because transduction at the time of grafting leads to rapid loss of transgene expression, whereas delayed transduction yields durable transgene expression. 26
Figure 1 Study Protocols (A) Vein graft atherosclerosis study. Rabbits were begun on a 0.3% cholesterol diet.
…”
Section: Resultsmentioning
confidence: 99%
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“…We delayed transduction until 4 weeks after grafting because transduction at the time of grafting leads to rapid loss of transgene expression, whereas delayed transduction yields durable transgene expression. 26
Figure 1 Study Protocols (A) Vein graft atherosclerosis study. Rabbits were begun on a 0.3% cholesterol diet.
…”
Section: Resultsmentioning
confidence: 99%
“…In our previous work and in results reported by others, incubation of adenovirus in a vein lumen followed by grafting of the vein results in transgene expression that is largely confined to luminal endothelial cells. 26 , 38 , 39 , 40 , 41 Other groups have reported transgene expression in the venous media and adventitia, but this may be due to variability in technique. 42 , 43 , 44 Based on our previous work with vein grafts of chow-fed rabbits 26 and our finding that hyperlipidemia does not alter the endothelial predominance of transgene expression in adenovirus-infused arteries, 29 we assume that most HDAdNull genomes (if they are intracellular) are likely within luminal endothelial cells.…”
Section: Resultsmentioning
confidence: 99%
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“…Here we tested several strategies aimed either at increasing HDAd-mediated apo A-I expression in EC at all time points or at stabilizing apo A-I expression between day 3 and day 28 after gene transfer (after day 28 HDAd appears to express apo A-I indefinitely in EC). [11][12][13] We first sought to increase translation of transgene mRNA by using species-specific codonoptimized transgene sequences. We next attempted to increase transgene mRNA stability by removing endogenous 3¢-untranslated (UTR) sequences.…”
Section: Introductionmentioning
confidence: 99%