Martina Yuri, Avitabile Daniele, Piersanti Stefania, Cherubini Gioia, Saggio Isabella
Department of Genetics and Molecular Biology, University La Sapienza, and Fondazione Parco Biomedico S. Raffaele, Rome, Italy.
Virus Res. 2007 Dec;130(1-2):71-84. doi: 10.1016/j.virusres.2007.05.019. Epub 2007 Jun 29.
One problem encountered in the use of adenoviral vectors for gene therapy is their toxicity. Although many studies have analyzed this question in vivo, few researches have investigated adenovirus vector effects at the cellular level using a large-scale approach. In particular, no such data are available for helper-dependent adenovirus vectors (HD), which are promising adenovirus vectors for clinical applications since they are devoid of all viral genes and can host large transgene cassettes. The present study used gene chips to examine (Affymetrix HG-U95Av2 interrogating 12,626 unique human transcripts) the effect on liver cells of HD vectors versus that of DeltaE1/E3 adenovirus vector and wild type Adenovirus (Ad5). The effects of the DeltaE1/E3 adenovirus and of HD vectors were comparable, and significantly milder than that of Ad5. Interestingly the expression signatures of DeltaE1/E3 adenovirus and HD vectors were non-overlapping both at the single gene and the pathway level, suggesting specific and different interactions between the host cell and the two gene therapy vectors.
在使用腺病毒载体进行基因治疗时遇到的一个问题是它们的毒性。尽管许多研究已经在体内分析了这个问题，但很少有研究使用大规模方法在细胞水平上研究腺病毒载体的作用。特别是，对于依赖辅助病毒的腺病毒载体（HD），目前还没有这样的数据，这种载体是很有前景的临床应用腺病毒载体，因为它们不含所有病毒基因，并且可以容纳大的转基因盒。本研究使用基因芯片（Affymetrix HG-U95Av2检测12,626个独特的人类转录本）来检测HD载体对肝细胞的影响，并与缺失E1/E3区的腺病毒载体和野生型腺病毒（Ad5）进行比较。缺失E1/E3区的腺病毒和HD载体的影响相当，并且明显比Ad5的影响要轻。有趣的是，缺失E1/E3区的腺病毒和HD载体的表达特征在单个基因和通路水平上都不重叠，这表明宿主细胞与这两种基因治疗载体之间存在特定且不同的相互作用。
