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Exclusive: Gates Foundation backs startup using optogenetics to manufacture biologics

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A biotech startup called Prolific Machines believes that it can help cut manufacturing costs with carefully choreographed light shows that coax cells to keep pumping out drugs. And now it’s got backing from one of the biggest public health funders to prove it.

The Bill & Melinda Gates Foundation is giving the Emeryville, CA-based company a $2 million grant to figure out how to make monoclonal antibodies for infectious disease affordable for low- and middle-income countries, the startup told Endpoints News exclusively.

Biologic drugs, including antibodies and other proteins produced from vats of living cells, are expensive to manufacture, with some estimates around $100 to $200 per gram. Prolific is aiming to lower costs to $10 per gram.

Deniz Kent

The startup’s idea is a twist on optogenetics techniques that have swept neuroscience labs over the past decade. Light-sensitive ion channels borrowed from algae and genetically implanted in neurons have given researchers a way to turn specific brain cells or regions on or off in the lab. Prolific aims to expand the method by using light to control gene expression, metabolism and other functions in cells.

“It felt like there was so much more that optogenetics could do,” Deniz Kent, the startup’s co-founder and CEO, told Endpoints in an interview. “And manufacturing was ripe with opportunities.”

Biomanufacturers often rely on cocktails of small molecules and proteins to subvert cells and get them to crank out drugs. But these can be expensive and can be tricky to fine-tune. “You can’t control when it goes, or where it goes, and it tends to perturb the entire system,” Kent said.

Light offers a more precise alternative. It can be turned on and off with the flick of a switch. It can be easily cast across an entire mass of cells or laser-focused on certain ones. And different colors of light can control different optogenetic switches installed in the same cell.

A brighter way to make drugs

The Gates grant comes about two months after the startup raised a $55 million Series B. The venture capital arm of dairy giant Fonterra led that round, which spotlighted Prolific’s claims that its methods could also help make lab-grown meat more affordable.

But Kent told Endpoints that Prolific isn’t a food company, and it doesn’t plan on making its meat, or even drugs, in-house. Instead, it will build and sell the optogenetic tools to control cells, the hardware to illuminate and monitor cells, and software to choreograph and optimize the light show.

“Once you have that toolkit, you can put it into a bovine cell line and make food, you can put it into a CHO cell line and make antibodies, or you can put it into a HEK cell line and make AAVs. It doesn’t really matter,” Kent said. But Prolific’s biggest customers will be pharma companies and contract manufacturers, he said.

While most optogenetics work in neuroscience is based on proteins called opsins, which change the electric charge of brain cells, Prolific is focused on a different class of light-sensitive molecules broadly known as dimerization switches. When exposed to light, these proteins change shape and hold onto each other.

“We take advantage of that by genetically tethering them to various different targets inside cells,” Kent said. “All of our tools just bring things together and then separate them out using light.”

He’s especially excited about using optogenetics to boost the production of tough-to-manufacture proteins and said the company has found a way to enlarge two cell organelles — the endoplasmic reticulum and Golgi apparatus — to boost the production and secretion of proteins.

Prolific has got cells to use their energy more efficiently, pump out protein drugs more continuously, and keep cells healthier for longer, Kent said. But the company isn’t discussing the details of how that approach works.


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