New cell programming technology transforms bacteria into efficient biotech factories

Frustrated by the length of time it takes to perform DNA sequencing, a team of researchers at Harvard Medical School have developed a new cell programming method that allows them to edit multiple genes in parallel instead of targeting one gene at a time. The new cell programming method called Multiplex Automated Genome Engineering (MAGE) promises to give synthetic biology a "powerful boost."

"We initiated the project to close the gap between DNA sequencing technology and cell programming technology," explains graduate student Harris Wang, the paper's co-first author. And adds postdoctoral researcher Farren Isaacs, the other first author, "The goal was to use information gleaned from genetics and genomics to rapidly engineer new functions and improve existing functions in cells. We wanted to develop a new tool and demonstrate how to apply it; we were determined to hand labs a hammer and a nail."

Why was the development of a new tool so important? With high-throughput sequencing, biologists have been able to scan millions of DNA letters, or bases, every hour. However, when having to revise a genome, they have been seriously impeded by outdated cell programming technology, getting bogged down with particular DNA sequences. The key was to find a way to "break free" of linear genetic engineering techniques in order to move past the serial manipulation of single genes.

The researchers accomplished this by rapidly refining the design of a bacterium. The MAGE programming method has enabled them to edit multiple genes in parallel instead of targeting one gene at a time. In essence, they transformed self-serving E. coli cells into "efficient factories" that produce a specific compound, reducing what normally takes most biotech companies months, if not years, into just three days.

"It's nearly impossible to predict which combinations of mutations will confer the desired behavior," explains Isaacs. "Biology is so complex that we don't know the optimal solution." As Wang notes, the team has “retooled evolution," generating genetic diversity at an incredibly fast rate to increase their odds of finding cells with desirable properties. "We accelerated evolution, generating as many as 15 billion genetic variants in three days," says Wang. "Can you imagine how long it would take to generate 15 billion genetic variants with traditional cloning techniques? It would take years."

News Release: Researchers Rapidly Turn Bacteria Into Biotech Factories www.sciencedaily.com July 26, 2009

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