Monday, November 22, 2010

MAGE (multiplex automated genetic engineering) technique developed from university research promises to speed up cellular mutations

Dr. George Church, a synthetic biologist and Harvard Medical School professor, says he can create living things faster than nature can, essentially speeding up evolution. And he says he can do it cheaply.

That intrigues us at STINSON Brand Innovation, and it’s another example of creative university discovery poised for development for broader biomedical use.

Most synthetic biologists laboriously tweak a genome one small piece at a time, then look at how the new cell behaves. Dr. Church, and fellow researchers Farren Isaacs and Harris Wang, have invented a technology known as multiplex automated genetic engineering, or MAGE, which makes the process much faster.

The table-top machine they created allows researchers to make 50 different genome alterations at nearly the same time. Combined with the mutations that occur as those cells go on and reproduce, MAGE can create billions of cellular mutations in a matter of days, essentially speeding up evolution. Scientists can then identify the most useful mutations.

Church’s team was able to genetically alter a common bacterium, E. coli, to produce lycopene, an antioxidant in tomatoes that may help fight cancer. Some of the altered bacteria produced five times the normal quantity of lycopene. The team spent just three days and $1,000 in supplies to produce the bacteria. Using old techniques, it would have taken months, says Church.

Church says his MAGE device will go on sale later this year for about $90,000. And at least a dozen companies, including DuPont and biotech startup Amyris, are considering purchasing it, says Wang.

Take a look at this quote from Church’s paper on MAGE:

Programming cells by multiplex genome engineering and accelerated evolution. Nature 460, 894-898 (13 August 2009).

“Here, we describe multiplex automated genome engineering (MAGE) for large-scale programming and evolution of cells. MAGE simultaneously targets many locations on the chromosome for modification in a single cell or across a population of cells, thus producing combinatorial genomic diversity. Because the process is cyclical and scalable, we constructed prototype devices that automate the MAGE technology to facilitate rapid and continuous generation of a diverse set of genetic changes (mismatches, insertions, deletions). We applied MAGE to optimize the 1-deoxy-d-xylulose-5-phosphate (DXP) biosynthesis pathway in Escherichia coli to overproduce the industrially important isoprenoid lycopene. Twenty-four genetic components in the DXP pathway were modified simultaneously using a complex pool of synthetic DNA, creating over 4.3 billion combinatorial genomic variants per day.”

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