Foamy virus–adenovirus hybrid vectors
Foamy virus–adenovirus hybrid vectors
复制标题
DOI：
10.1038/sj.gt.3302216
复制
发表时间：
2004-04
期刊：
影响因子：
5.1
通讯作者：
M. Picard-Maureau;F. Kreppel;Dirk Lindemann;T. Juretzek;O. Herchenröder;A. Rethwilm;Stefan Kochanek;M. Heinkelein
中科院分区：
文献类型：
--
作者：
M. Picard-Maureau;F. Kreppel;Dirk Lindemann;T. Juretzek;O. Herchenröder;A. Rethwilm;Stefan Kochanek;M. Heinkelein
为了赋予腺病毒载体（AdV）整合到宿主细胞基因组中的特征，在体外表征了杂合载体，其在高容量AdV的骨架中表达衍生自原型泡沫病毒（FV）的载体。FV构成具有独特复制途径且没有已知致病性的逆转录病毒亚家族。在没有包膜糖蛋白的情况下，原型FV表现得像逆转录转座子，而在其存在下表现得像外源性逆转录病毒。构建了两种主要类型的载体，其允许细胞内（HC-FAD-7）或另外的细胞外（HC-FAD-2）途径。在两种嵌合体中，FV载体的表达由四环素可调节系统控制。杂交产生接近10 - 10感染单位/ml。通过Southern印迹，显示了杂交载体产生宿主细胞基因组整合体的功能。然而，HC-FAD-7建立稳定的转基因表达的效率相当低，而在用HC-FAD-2以100的MOI初次转导后的第二轮中，约70%的细胞被稳定地转导。鉴于高容量腺病毒和FV载体的良性特性，基于HC-FAD-2的杂交体可能适合于体内应用。
To confer adenovirus vectors (AdV), the feature of integration into the host cell genome hybrid vectors were characterized in vitro, which express vectors derived from the prototypic foamy virus (FV) in the backbone of a high-capacity AdV. FVs constitute a subfamily of retroviruses with a distinct replication pathway and no known pathogenicity. In the absence of envelope glycoprotein, the prototypic FV behaves like a retrotransposon, while it behaves like an exogenous retrovirus in its presence. Two principle types of vectors, which either allows the intracellular (HC-FAD-7) or, in addition, the extracellular (HC-FAD-2) pathway were constructed. In both chimeras the expression of the FV vector was controlled by the tetracycline-regulatable system. Hybrids were produced close to 10 10 infectious units/ml. By Southern blotting, the functionality of the hybrid vectors to generate host cell genomic integrants was shown. However, the efficiency of HC-FAD-7 to establish stable transgene expression was rather low, while around 70% of cells were stably transduced in secondary round following primary transduction with HC-FAD-2 at an MOI of 100. Given the benign characteristics of high-capacity adenovirus and FV vectors, hybrids based on HC-FAD-2 are probably suited for an in vivo application.