Grassi G, Köhn H, Dapas B, Farra R, Platz J, Engel S, Cjsareck S, Kandolf R, Teutsch C, Klima R, Triolo G, Kuhn A
Department of Molecular Pathology, University Hospital of Tübingen, Tübingen, Germany.
Arch Virol. 2006 Feb;151(2):255-71. doi: 10.1007/s00705-005-0636-4. Epub 2005 Sep 30.
The development of effective gene-therapeutic applications for cardiovascular disorders is in part limited by the lack of appropriate delivery systems. In an attempt to overcome this deficiency, we investigated the ability of baculoviral vectors to transduce human cardiovascular cells, for which data are missing in literature. Additionally, baculovirus ability to transduce target cells was compared to that of an adenoviral vector, a well characterized and widely used viral vector. Transduction experiments, performed using baculo/adenoviral vectors expressing the enhanced green fluorescence protein, revealed that, under the experimental condition considered, baculoviruses but not adenoviruses efficiently transduce human coronary smooth muscle cells (hCSMC); an opposite behavior was noticed for human coronary endothelial cells (hCEC). Thus, baculoviral vectors are potentially indicated as transfer system in the treatment of coronary restenosis, where growth inhibitory genes should reach hCSMC but not hCEC. When used to transduce human cardiomyocytes and fibroblasts, both vectors behaved similarly. Finally, studies on cellular DNA replication revealed a more prolonged and pronounced negative effect on cells transduced by adenoviral compared to baculoviral vectors. Our data indicate that baculoviruses represent an attractive alternative to adenoviruses as transfer vectors in cardiovascular cells and that baculovirus have the potential to be used as gene transfer system in cardiovascular diseases such as restenosis.
用于心血管疾病的有效基因治疗应用的发展在一定程度上受到缺乏合适递送系统的限制。为了克服这一缺陷,我们研究了杆状病毒载体转导人心血管细胞的能力,而文献中缺少相关数据。此外,将杆状病毒转导靶细胞的能力与腺病毒载体(一种特征明确且广泛使用的病毒载体)的能力进行了比较。使用表达增强型绿色荧光蛋白的杆状/腺病毒载体进行的转导实验表明,在所考虑的实验条件下,杆状病毒而非腺病毒能有效地转导人冠状动脉平滑肌细胞(hCSMC);而人冠状动脉内皮细胞(hCEC)则表现出相反的行为。因此,杆状病毒载体可能被用作治疗冠状动脉再狭窄的转移系统,在这种情况下,生长抑制基因应作用于hCSMC而非hCEC。当用于转导人心肌细胞和成纤维细胞时,两种载体的表现相似。最后,对细胞DNA复制的研究表明,与杆状病毒载体相比,腺病毒载体对转导细胞的负面影响更持久、更明显。我们的数据表明,杆状病毒作为心血管细胞中的转移载体是腺病毒的一个有吸引力的替代选择,并且杆状病毒有潜力被用作冠状动脉再狭窄等心血管疾病的基因转移系统。