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Chemical synthesis of poliovirus cDNA: Generation of infectious virus in the absence of natural template

First ever virus synthesized from chemicals alone.

Chemicals and a computer: all you need to make a virus. Credit: © GettyImages

Using genetic code as the recipe and carbon-containing chemicals as ingredients, researchers have made infective poliovirus entirely from scratch. This is the first time that a working biological entity has been made using chemistry alone.

The team behind the achievement claim that it demonstrates the risk of further viruses being created from just their genetic code - by bioterrorists, for example. Other virologists are sceptical.

Compared with living things such as bacteria, animals and plants, viruses are rudimentary - even their status as organisms is debated. Building complex life forms from scratch, at least using current technology, is still regarded as impossible.

Eckard Wimmer of the State University of New York in Stony Brook and his colleagues assembled large chunks of the poliovirus genome by joining up the four chemical subunits of DNA in the correct sequence. They put this synthetic virus genome into "cell juice" - a mixture of protein-building molecules and catalysts - and watched the virus assemble itself1.

The re-engineered virus infected mouse cells just as a normal poliovirus would and successfully replicated itself in them.

"It's a beautiful study," says virologist Olen Kew of the US Centers for Disease Control in Atlanta, Georgia. The individual steps of Wimmer's process, such as manufacturing the sequence, and growing a virus outside a cell, had been demonstrated before. "The strength of this study is its having strung them all together," explains Kew.

Open season?

The gene sequences for ebola, influenza, smallpox, HIV and many other viruses are publicly available on the Internet. Wimmer argues that it could now be open season for rogue virus engineers. "You can make any virus from published data," he says.

To do this with larger viruses would be very difficult indeed Olen Kew , US Centers for

But poliovirus is easier to build than many others. It has a very short and simple genome and assembles itself directly from a DNA template; others go through intermediate translation stages.

More complex viruses could be synthesized, Wimmer believes, by additional chemical steps, or by putting synthetic gene sequences into living cells.

The likelihood of anyone trying this is tiny, thinks Kew. The poliovirus genome is 7,500 subunits long; that of smallpox is more than 24 times longer. Synthesizing larger viruses from scratch would be "very difficult indeed", he says. Making the building blocks would demand new technologies and lots of money.

"This is not something you could do in your garden shed," agrees Neil Berry, who studies HIV at Britain's National Institute for Biological Standards and Control in Potters Bar.

Even for a small virus such as HIV, there is hardly any need. "Nature has got a head start on us," Berry explains. Most pathogenic viruses are already present in the environment, and making one as virulent as a wild form would be nigh on impossible.

Says Kew: "Once any new sequence is published it's clear the virus can be recovered but we've assumed that for about 20 years".

References

  1. Cello, J., >Paul, A.V. & Wimmer, E. Chemical synthesis of poliovirus cDNA: Generation of infectious virus in the absence of natural template. Science published online, doi:10.1126/science.1072266 (2002).

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Chemical synthesis of poliovirus cDNA: Generation of infectious virus in the absence of natural template. Nature (2002). https://doi.org/10.1038/news020708-17

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