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Cell Therapy

Pump Up The Volume: ‘Genome Sculpting’ Could Help Scale Biotherapeutic Medicine

March 15, 2017
The first biopharmaceutical drugs using complex organic molecules produced by genetically modified cells to deliver more efficient therapies have already started to write the next chapter of medicine. Treatments designed from lab-made versions of large proteins are now being used to treat cancers and autoimmune disorders like multiple sclerosis. Research shows they might also do well against infectious diseases.
But there is still a lot of ground to cover before such treatments truly take off. Making these targeted therapies is still a slow, inefficient and expensive process. “The industry has progressed at a tremendous rate over the last couple of years, but it is still very expensive to make these protein drugs,” says Nicole Borth, the head of cell design and engineering at the Austrian Center of Industrial Biotechnology (acib) in Vienna. “In many countries, people who need them can’t afford them. Even in the U.S. and Europe, they quickly become too expensive for health systems as the number of patients and applications increase.”

Why? Biotherapeutics are generated in batches of genetically engineered living cells used as biofactories to pump out the desired proteins in maximum quantities. Scientists must get the cells to reproduce fast enough to fill large bioreactor tanks, and, at the end of the process, they need to extract the right molecules from the protein soup and purify them before they can be used safely. The whole process of arriving at an efficient production solution can easily last eight months. “It’s a tremendous workload fraught with uncertainty,” Borth says.

“The industry has progressed at a tremendous rate over the last couple of years, but it is still very expensive to make these protein drugs,” says acib's Nicole Borth. Images credit: GE Healthcare Life Sciences

That’s the reason behind Borth’s collaboration with GE Healthcare Life Sciences. The acib team and GE will be looking for ways to make the cellular biofactories produce more of the targeted therapeutic proteins faster and with less effort being put into finding suitable cells. If their work is successful, the process will hopefully become more efficient and reliable and cheaper.

In the short term, the group will be looking for the right tools and methods to manipulate the cells in a way that can optimize production. This involves tinkering with the process cells use to turn their DNA code into proteins. In the long term, the teams will work on creating a toolbox of predesigned cellular factories that are tailored for different classes of therapeutic proteins to speed up the path to production. “What we are aiming for in this collaboration is to develop the ability to manipulate cell behavior in an efficient way, such that we can design, define and control these properties and adapt them to whatever is best suited for a given product,” Borth says.

Daniel Ivansson, one of the researchers at GE Healthcare working on the project, says his company will be providing high-quality growth media, starter cells and gene transfer strategies in the hope of finding a new process that dramatically speeds the path to efficient production of any new protein drug. “We think of this work as ‘genome sculpting’ — trying to get these cells into an overdrive state that optimizes industrial therapeutics production,” he says. “We want to establish a new methodology to sculpt the genome into efficient states, thus raising the bar on productivity.”

Borth says the collaboration could have a dramatic impact, cutting production time in half or more and reducing the workload for scientists monitoring the cellular manufacturing process by 90 percent. Ivansson agreed, adding that such improvements would serve to boost innovation of more new drugs.

“Reducing the workload so much could also open up time that researchers would otherwise dedicate to improving the production process, thus enabling the search for more new molecules,” he says. “You can find many more molecules if you have time to test more.”