Studies of virus particles and the steps in their life cycle have spearheaded our understanding of biological systems at the molecular level. These studies, however, relied on virus specimens isolated from nature. This dependency changed forever in 2002 when the chemical synthesis of poliovirus, in the absence of any natural template, was published. The work caused a shock wave because it led to excitement as well as revulsion, reflecting the new reality that, for better or worse, all of the more than 2,000 viruses whose genome sequences are deposited by the National Center for Biotechnology Information can be recreated in the laboratory in the absence of natural isolates. So what have we learned?
Synthetic poliovirus and other designer viruses: what have we learned from them? (2011) Annu Rev Microbiol. 65:583-609
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.