Made-to-order viral genomes came a step closer to reality today. Molecular biologists announced that, in just 2 weeks, they had assembled an artificial bacterial virus from its components. The virus was able to infect and kill bacteria almost as well as the real thing. The achievement, while celebrated as a major step forward in synthetic biology, could also make it easier for bioterrorists to make dangerous pathogens.

Handmade. Spots on this petri dish consist of viruses with artificial genomes. CREDIT: PNAS

Ever since researchers began deciphering DNA, they have wondered if they could use the sequences to build synthetic genomes. Living cells reproduce their genomes by working off an existing copy of the DNA. But it’s also possible to stitch a genome together a few bases at a time, a team of biologists led by molecular virologist Eckard Wimmer of the State University of New York, Stony Brook, concluded last year, after having assembled the polio virus from scratch (Science, 9 August 2002, p. 1016). But the task was laborious, and the genome took 3 years to construct.

That's too long, thought genome pioneer J. Craig Venter, head of the Institute for Biological Energy Alternatives (IBEA) in Rockville, Maryland, which envisions custom-designed microbes that can get rid of excess carbon dioxide and clean up toxic wasters. So with IBEA collaborators Hamilton Smith and Cynthia Pfannkoch, and Clyde Hutchinson from the University of North Carolina, Chapel Hill, Venter set out to develop a faster and more accurate approach toward making artificial genomes. At a press conference today at the Department of Energy, which funded the work, the team announced that they have succeeded.

The researchers first produced short pieces of single-stranded DNA. They then put the short strands together, matching up overlapping ends of each strand to get a single template for the entire genome. A modified version of the polymerase chain reaction--a commonly used technique used to copy small pieces of DNA--enabled them to build the complete two-stranded chromosome. The virus readily infected bacteria, hijacking their genetic machinery to duplicate itself. "It's a very smart piece of work," says Wimmer--although he notes that it could renew concerns about the possibility of producing bioterror viruses from scratch.

The viral genome was only 5000 base pairs. But Venter plans to scale up this process by combining many 5000-base pieces to make larger genomes; IBEA's ultimate goal is to produce a small bacterial cell from scratch. But Wimmer points out that in order to build a bacterium, the genome has to be put into a cell, which is a much tougher job.

--ELIZABETH PENNISI

Related sites
Web site for the Department of Energy program that supports Venter and other genome-related projects
Series of lectures on the biology of phages (PDF)