Saha Bratati, Wong Carmen M, Parks Robin J
Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, Ontario K1H 8L6, Canada.
Viruses. 2014 Sep 24;6(9):3563-83. doi: 10.3390/v6093563.
Adenovirus (Ad) vectors are currently the most commonly used platform for therapeutic gene delivery in human gene therapy clinical trials. Although these vectors are effective, many researchers seek to further improve the safety and efficacy of Ad-based vectors through detailed characterization of basic Ad biology relevant to its function as a vector system. Most Ad vectors are deleted of key, or all, viral protein coding sequences, which functions to not only prevent virus replication but also increase the cloning capacity of the vector for foreign DNA. However, radical modifications to the genome size significantly decreases virion stability, suggesting that the virus genome plays a role in maintaining the physical stability of the Ad virion. Indeed, a similar relationship between genome size and virion stability has been noted for many viruses. This review discusses the impact of the genome size on Ad virion stability and emphasizes the need to consider this aspect of virus biology in Ad-based vector design.
腺病毒(Ad)载体是目前人类基因治疗临床试验中最常用的治疗性基因递送平台。尽管这些载体很有效,但许多研究人员试图通过详细表征与作为载体系统功能相关的腺病毒基本生物学特性,来进一步提高基于腺病毒载体的安全性和有效性。大多数腺病毒载体删除了关键或所有病毒蛋白编码序列,这不仅起到防止病毒复制的作用,还增加了载体对外源DNA的克隆能力。然而,对基因组大小的根本性改变会显著降低病毒粒子的稳定性,这表明病毒基因组在维持腺病毒病毒粒子的物理稳定性方面发挥着作用。事实上,许多病毒都存在基因组大小与病毒粒子稳定性之间的类似关系。本文综述讨论了基因组大小对腺病毒病毒粒子稳定性的影响,并强调在基于腺病毒的载体设计中需要考虑病毒生物学的这一方面。