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These Synthetic Snippets Of DNA Could Make A New Generation Of Drugs Available To All

There’s more to protein than steak, eggs and the South Beach Diet. The complex molecules encoded by our DNA are the workhorses of our cells, being responsible for growth, maintenance and repair.

The human body holds many thousands of different proteins, and even small typos in the genetic code can lead to diseases and conditions such as diabetes, hemophilia, dwarfism and many others.

A new class of drugs called biopharmaceuticals that deliver the working version of the protein into the body can manage some of these afflictions. As of last year, more than 650 protein drugs had been approved around the world, and at least 1,300 more are now under development, according to one study. They include bestselling therapeutics such as Herceptin and Prevnar and are expected to account for half of all new therapies by 2020.

The problem is that biopharmaceuticals cost a lot of money. That’s partly because drug companies generate the proteins in specially engineered cells and their construction is a delicate and slow operation whose science is still being worked out.

But researchers at the Scottish company Synpromics have been able to develop tools that can increase the efficiency and robustness of the process. Their solution hinges on so-called promoters, short strands of DNA sitting on the chromosome right next to important protein-producing genes. Promoters tell cellular machinery floating in the cell’s nucleus that the gene is next door and to start using it. They are also involved in controlling the flow of proteins any one cell pumps out.

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Top and above: GE’s facility in Uppsala is one of the world’s biggest production facilities for manufacturing of chromatography media for the biologics industry. Images credit: GE Healthcare Life Sciences

But the way promoters naturally work in cells is not efficient for industrial production. So Synpromics harnessed the new field of synthetic biology to create synthetic promoters. The company takes pieces of the natural promoters that have evolved in cells over millions of years and splices them together. These laboratory-arranged blocks of DNA allow the creation of a toolbox of synthetic promoters that make protein production more precise and enable the company to control the expression more effectively in the industrial setting.

“Promoters the biopharmaceutical industry uses today are derived from viruses, which work faster but can’t be customized,” says Michael Roberts, a biochemist who founded Synpromics and who is its chief scientific officer. “We make our synthetic promoters from natural ones, looking for various elements that are active and bringing them together. This leverages what cells have already optimized through evolution and makes them more efficient. It really drives gene expression to a commercial scale.”

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A bioreactor tank used in the production of biopharmaceuticals. Image credit GE Healthcare Life Sciences.

Synpromics’ innovation has been attracting attention within the life-sciences community. Seeing the commercial potential, GE Healthcare has entered into a research agreement with the biotech startup. The two companies will develop a platform that will enable customers to produce industrial quantities of biopharmaceuticals with the technology. As part of the collaboration, Synpromics will create synthetic promoters specifically built to improve the performance of GE Healthcare’s cellular production platform. GE then will have the option to take the technology to customers in the biopharmaceuticals sector.

Daniel Ivansson, a GE Healthcare researcher, said GE has been looking for ways to make the protein synthesis process that’s specific to creating protein drugs more efficient and increase production. “Their product helps biopharmaceutical production become more of an engineering discipline, where it used to be more of an art,” he says. “It really is cutting-edge technology that Synpromics has, and it’s one part of the puzzle to help biotherapeutics move forward.”

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