Synthetic viruses: a new opportunity to understand and prevent viral disease.

Synthetic viruses: a new opportunity to understand and prevent viral disease.
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DOI:
10.1038/nbt.1593
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发表时间:
2009-12
影响因子:
46.9
通讯作者:
--
中科院分区:
工程技术1区
文献类型:
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DNA合成和测序的快速进展引领着对生物体进行有意的、大规模的基因改变。DNA操作方面的这些新进展已扩展到全基因组合成水平,脊髓灰质炎病毒的合成、1918年已灭绝的流感病毒株和人类内源性逆转录病毒株的复活以及噬菌体T7基因组的重组都证明了这一点。迄今为止合成的最大的DNA是生殖支原体的582,970碱基对基因组,尽管到目前为止,这个合成DNA还没有被“启动”到生命中。由于基因组合成是独立于自然模板的,它允许对病毒遗传信息的结构和功能进行迄今为止不可能的修改。这种新策略的共同目标是进一步了解生物体的特性,特别是它的致病武器库,如果它引起人类疾病,并利用这些新信息来预防或治疗人类病毒性疾病。虽然迄今为止只描述了几种病毒合成的应用,但最近的主要发现是1918年流感病毒的复活以及密码子和密码子对失优的脊髓灰质炎病毒的产生。
Rapid progress in DNA synthesis and sequencing is spearheading the deliberate, large-scale genetic alteration of organisms. These new advances in DNA manipulation have been extended to the level of whole-genome synthesis, as evident from the synthesis of poliovirus, from the resurrection of the extinct 1918 strain of influenza virus and of human endogenous retroviruses and from the restructuring of the phage T7 genome. The largest DNA synthesized so far is the 582,970 base pair genome of Mycoplasma genitalium, although, as yet, this synthetic DNA has not been 'booted' to life. As genome synthesis is independent of a natural template, it allows modification of the structure and function of a virus's genetic information to an extent that was hitherto impossible. The common goal of this new strategy is to further our understanding of an organism's properties, particularly its pathogenic armory if it causes disease in humans, and to make use of this new information to protect from, or treat, human viral disease. Although only a few applications of virus synthesis have been described as yet, key recent findings have been the resurrection of the 1918 influenza virus and the generation of codon- and codon pair–deoptimized polioviruses.