Adeno-associated virus: a key to the human genome?
Adeno-associated virus: a key to the human genome?
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DOI：
10.2217/fvl.10.48
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发表时间：
2010-09-01
期刊：
影响因子：
3.1
通讯作者：
Linden RM
中科院分区：
文献类型：
--
作者：
Henckaerts E;Linden RM
腺相关病毒（AAV）广泛传播于整个人群，但没有病理学与感染相关。这一事实，加上简单的分子技术来改变包装的病毒基因组的可用性，使AAV成为寻找理想的基因治疗载体的有力竞争者。然而，我们对这种病毒有趣特征的理解还远远没有耗尽，很可能病毒生活方式的机制将揭示可能的新策略，可用于未来的临床方法。一个这样的方面是AAV为了建立潜伏期而发展的独特方法。在不存在将支持生产性病毒复制的细胞环境的情况下，野生型AAV可以将其基因组位点特异性地整合到人染色体19上的基因座（称为AAVS1）中，在那里它驻留而对宿主细胞没有明显影响，直到细胞条件被外部影响改变，例如腺病毒超感染，这将导致病毒基因组的拯救和生产性复制。本文将介绍AAV的生物学，靶向基因组整合的独特病毒策略，并在试图建立利用靶向基因添加到人类基因组的治疗方法的背景下解决相关问题。
Adeno-associated viruses (AAV) are widely spread throughout the human population, yet no pathology has been associated with infection. This fact, together with the availability of simple molecular techniques to alter the packaged viral genome, has made AAV a serious contender in the search for an ideal gene therapy delivery vehicle. However, our understanding of the intriguing features of this virus is far from exhausted and it is likely that the mechanisms underlying the viral lifestyle will reveal possible novel strategies that can be employed in future clinical approaches. One such aspect is the unique approach AAV has evolved in order to establish latency. In the absence of a cellular milieu that will support productive viral replication, wild-type AAV can integrate its genome site specifically into a locus on human chromosome 19 (termed AAVS1), where it resides without apparent effects on the host cell until cellular conditions are changed by outside influences, such as adenovirus super-infection, which will lead to the rescue of the viral genome and productive replication. This article will introduce the biology of AAV, the unique viral strategy of targeted genome integration and address relevant questions within the context of attempts to establish therapeutic approaches that will utilize targeted gene addition to the human genome.
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