Fibrin scaffold promotes adenoviral gene transfer and controlled vector delivery
Fibrin scaffold promotes adenoviral gene transfer and controlled vector delivery
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DOI：
10.1002/jbm.a.32039
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发表时间：
2009-06-15
影响因子：
4.9
通讯作者：
Pandit, Abhay
中科院分区：
文献类型：
--
作者：
Breen, Ailish;Dockery, Peter;Pandit, Abhay
在组织再生中使用腺病毒载体的基因治疗受到转基因表达持续时间短的阻碍。假设纤维蛋白支架将增强腺病毒向伤口部位的递送，从而排除对高重复剂量的需要。其目的是分析纤维蛋白是否可以将低单剂量的病毒载体递送到伤口部位，而不影响转染效率。将含有编码β-半乳糖苷酶的腺病毒的纤维蛋白支架、单独的纤维蛋白、单独的腺病毒和无治疗组应用于兔耳溃疡模型。在第7天和第14天测量β-半乳糖苷酶转基因表达。在第7天，含纤维蛋白的腺病毒组中转基因表达增强。到第14天，表达较低，组间无差异。评估伤口愈合的体视学方法旨在确定腺病毒衣壳是否引起不利的炎症反应，以及纤维蛋白的有益性质是否因加入腺病毒而改变。纤维蛋白腺病毒组显示出与单独的纤维蛋白相似的伤口愈合反应，在第7天显示出最大的细胞结构和血管生成。到第14天，细胞和血管生成消退，并且这种作用不受腺病毒存在的抑制。单独的腺病毒不会引起不利的炎症反应。结论是纤维蛋白有助于低剂量病毒载体的递送，从而避免慢性炎症反应，并且允许比单独的病毒载体更上级的转染。这对在组织工程中使用病毒载体具有广泛的影响。(c)2008 Wiley Periodicals，Inc.生物医学材料研究杂志89 A：876-884，2009年
Gene therapy using adenoviral vectors in tissue regeneration is hindered by a short duration of transgene expression. It is hypothesized that a fibrin scaffold will enhance delivery 4 the adenovirus to a wound site, precluding the need for high repeated doses. It was aimed to analyze whether fibrin could deliver a low single dose of viral vector to a wound site, without compromising transfection efficiency. Fibrin scaffold containing adenovirus encoding beta-galactosidase, fibrin alone, adenovirus alone, and no treatment groups were applied to a rabbit ear ulcer model. P-Galactosidase transgene expression was measured at 7 and 14 days. Transgene expression was enhanced in the fibrin containing adenovirus group at 7 days. By 14 days, there was low expression and no difference between groups. Stereological methods assessing Wound healing aimed to determine whether the adenovirus capsid elicited an unfavorable inflammatory response and whether fibrin's beneficial properties were altered by addition of adenovirus. The fibrin adenovirus group showed a wound-healing response similar to fibrin alone, showing maximum cellularity and angiogenesis at 7 days. By 14 days, cellularity and angiogenesis subsided, and this effect was not inhibited by the presence of adenovirus. Adenovirus alone did not Cause an unfavorable inflammatory response. It is concluded the fibrin aids in the delivery of a low-dose viral vector, thereby avoiding a chronic inflammatory response, and allowing superior transfection than viral vector alone. This has wide-ranging implications on the use of viral vectors in tissue engineering. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res 89A: 876-884, 2009