Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York 11790, USA.
Annu Rev Microbiol. 2011;65:583-609. doi: 10.1146/annurev-micro-090110-102957.
Owing to known genome sequences, modern strategies of DNA synthesis have made it possible to recreate in principle all known viruses independent of natural templates. We describe the first synthesis of a virus (poliovirus) in 2002 that was accomplished outside living cells. We comment on the reaction of laypeople and scientists to the work, which shaped the response to de novo syntheses of other viruses. We discuss those viruses that have been synthesized since 2002, among them viruses whose precise genome sequence had to be established by painstakingly stitching together pieces of sequence information, and viruses involved in zoonosis. Synthesizing viral genomes provides a powerful tool for studying gene function and the pathogenic potential of these organisms. It also allows modification of viral genomes to an extent hitherto unthinkable. Recoding of poliovirus and influenza virus to develop new vaccine candidates and refactoring the phage T7 DNA genome are discussed as examples.
由于已知的基因组序列,现代 DNA 合成策略使得独立于天然模板重建所有已知病毒成为可能。我们描述了 2002 年首次在活细胞外合成病毒(脊髓灰质炎病毒)的情况。我们评论了外行和科学家对这项工作的反应,这塑造了对其他病毒从头合成的反应。我们讨论了自 2002 年以来合成的病毒,其中包括那些必须通过艰苦地拼接序列信息片段才能确定其精确基因组序列的病毒,以及那些与动物传染病有关的病毒。合成病毒基因组为研究基因功能和这些生物体的致病潜力提供了强有力的工具。它还允许对病毒基因组进行以前难以想象的修改。我们讨论了对脊髓灰质炎病毒和流感病毒进行重新编码以开发新疫苗候选物,以及对噬菌体 T7 DNA 基因组进行重构的问题。