McCarty Douglas M, Young Samuel M, Samulski R Jude
School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Annu Rev Genet. 2004;38:819-45. doi: 10.1146/annurev.genet.37.110801.143717.
The driving interest in adeno-associated virus (AAV) has been its potential as a gene delivery vector. The early observation that AAV can establish a latent infection by integrating into the host chromosome has been central to this interest. However, chromosomal integration is a two-edged sword, imparting on one hand the ability to maintain the therapeutic gene in progeny cells, and on the other hand, the risk of mutations that are deleterious to the host. A clearer understanding of the mechanism and efficiency of AAV integration, in terms of contributing viral and host-cell factors and circumstances, will provide a context in which to evaluate these potential benefits and risks. Research to date suggests that AAV integration in any context is inefficient, and that the persistence of AAV gene delivery vectors in tissues is largely attributable to episomal genomes.
对腺相关病毒（AAV）的主要兴趣在于其作为基因递送载体的潜力。早期观察到AAV可通过整合到宿主染色体中来建立潜伏感染，这一观察结果一直是人们对其产生兴趣的核心。然而，染色体整合是一把双刃剑，一方面赋予了在子代细胞中维持治疗性基因的能力，另一方面也带来了对宿主有害的突变风险。更清楚地了解AAV整合的机制和效率，包括相关的病毒和宿主细胞因子及情况，将为评估这些潜在益处和风险提供背景。迄今为止的研究表明，在任何情况下AAV整合效率都很低，并且AAV基因递送载体在组织中的持久性很大程度上归因于游离型基因组。
