Use of DNA microarrays to monitor host response to virus and virus-derived gene therapy vectors.

Stefania Piersanti, Yuri Martina, Gioia Cherubini, Daniele Avitabile, Isabella Saggio
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引用次数: 23

Abstract

Given the biological complexity of viral infections, the variability of the host response, and the safety concerns related to viral-mediated gene transfer, recent studies have made use of DNA mircoarrays to integrate multi-layered experimental approaches aimed at completely clarifying virus-host interactions. Particular attention has been given to those viruses that are implicated in clinical use and/or in life-threatening diseases. Examples of such use can be divided into three main categories, including: (i) the use of microarrays to study viral expression; (ii) the use of microarrays to analyze the host response to viral infection; and (iii) the use of microarrays to characterize the host response to viral vector-mediated transduction. Significant information on virus- and viral vector-host interactions can be obtained with the microarray approach, including the recognition of master pathways of virally-induced responses, the identification of new target genes for specific viruses, and indications on the molecular toxicity of specific gene transfer vectors currently used for gene therapy trials (in particular, adeno-associated viruses and adenovirus-derived vectors). We predict that the development of accessible repositories containing most of the DNA microarray data on viral infections will certainly help to elucidate the puzzling pictures of different viral infections. This will be crucially important for the correct handling of viral diseases and the intelligent amelioration of viral vectors for gene therapy.

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利用DNA微阵列监测宿主对病毒和病毒衍生基因治疗载体的反应。
鉴于病毒感染的生物学复杂性、宿主反应的可变性以及与病毒介导的基因转移相关的安全性问题,最近的研究利用DNA微阵列整合多层实验方法,旨在完全阐明病毒与宿主的相互作用。对那些与临床使用和(或)危及生命的疾病有关的病毒给予了特别关注。这种使用的例子可以分为三大类,包括:(i)使用微阵列研究病毒表达;(ii)利用微阵列分析宿主对病毒感染的反应;(iii)使用微阵列来表征宿主对病毒载体介导转导的反应。通过微阵列方法可以获得关于病毒-和病毒载体-宿主相互作用的重要信息,包括识别病毒诱导反应的主要途径,识别特定病毒的新靶基因,以及目前用于基因治疗试验的特定基因转移载体(特别是腺相关病毒和腺病毒衍生载体)的分子毒性指示。我们预测,包含大多数病毒感染的DNA微阵列数据的可访问存储库的开发必将有助于阐明不同病毒感染的令人困惑的图片。这对于正确处理病毒性疾病和智能改进基因治疗的病毒载体至关重要。
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