By Vivienne Raper, PhD

Synthetic biology is poised to help biologics manufacturers scale up their processes with custom-programmed cells. That’s according to Ron Weiss, PhD, professor of synthetic biology at the Massachusetts Institute of Technology, and a pioneer in the field.

According to Weiss, his research group is already working to genetically engineer cells that can manufacture useful products that are ordinarily toxic to the cells at an industrial scale.

In the future, he says, synthetic biology (SynBio) will be used to create cells that can sense their own internal state during monoclonal antibody production, or can allow manufacturers to precisely control glycosylation.

“Biomanufacturing is an area where synthetic biology has great potential in terms of what it [has to] offer,” says Weiss.

According to Weiss, it’s not possible to scale up manufacturing if the product is toxic, as the cells used for production quickly die.

Engineered cell line

To overcome this problem, his team has engineered a cell line to go through a growth phase where they don’t manufacture the product. They only begin to produce the product, he says, when there’s a critical density of cells.

“Having control mechanisms, which automatically sense when production needs to be on, can have you overcome [this] practical problem,” says Weiss.

Other work, he adds, includes designing cells that can sense whether they’re producing product efficiently, and then modifying their own intercellular environment to be more suitable for growth.

The team has also done research on programming cells to control glycosylation during monoclonal antibody production.

“You really need to think about cells as fully modifiable by genetic programs to include things like sensors to detect RNA levels, protein levels, and gene expression. All these things are possible, and we’ve demonstrated many of them in the SynBio community,” he says.

Some of his published research was a collaboration with Pfizer, and he says that many of these bioprocessing capabilities are close to being implementable in current manufacturing.

However, their uptake will depend on whether existing bioprocesses need to be redesigned to incorporate the new cellular capabilities.

“I think with respect to [adding] these bioprocess capabilities, it’s probably [going to happen] sooner [rather than later]. It’s just a matter of understanding how these engineered systems fit within existing workflows.”

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