Rather than controlling cell function by adding expensive growth factors or other molecules to cell culture media in a bioreactor, California-based Prolific Machines exposes cells containing light sensitive proteins to light at specific wavelengths, a technique known as optogenetics.
This can activate or deactivate certain genes, proteins, or cellular pathways, delivering “unprecedented cellular control” in biomanufacturing, CEO Dr. Deniz Kent told AgFunderNews at the recent Future Food-Tech summit in San Francisco.
Light: Cheap, and inherently sterile
For decades, “We’ve been using molecules—whether chemicals or proteins—to control cells, and they come with a bunch of problems,” said Kent, a stem cell biologist who cofounded Prolific Machines in 2020 with physicist and biomedical scientist Max Huisman PhD and computer scientist and ML engineer Declan Jones.
In some cases, the issue is cost, he noted, with some growth factors used in therapeutic proteins (IGF, EGF), stem cell cultivation (FGF, TGF-β), tissue engineering (VEGF, PDGF), vaccine production (GM-CSF, IL-2) and gene therapy (FGF2, HGF) coming with hefty price tags.
But this is not the only problem, he said: “You can’t control where these molecules go, and when they go where they go. Another issue is sterility [any component added to a bioreactor increases the risk of contamination], plus there are reproducibility problems because some of these molecules are biological in nature and so they are not consistent.”
Light, by contrast, “is cheap, inherently sterile, reproducible, and can be controlled spatially and temporally,” he said.
Another advantage of using light rather than molecules added to cell culture media to direct cellular activities is that it can potentially reduce downstream processing and purification costs post-harvest, as there are fewer media components you need to ensure do not end up in your final product, he says.
How it works
In a nutshell, Prolific Machines takes light sensitive proteins [of which there are thousands] and genetically attaches them to different targets inside the cell, explained Kent. “What we’ve invented is a way for machines to control some cellular biology specifically for the first time.”
As the cells that Prolific Machines is focusing on are not naturally light sensitive, the only things that respond to light in the bioreactors are the targets that it has tagged with light sensitive proteins, enabling great precision, he said.
“The whole beauty of the system that we’ve built is that you can perturb one part of it without perturbing the entire system, which leads to a lack of control.”
He added: “So there’s three parts to what we do. The first part is we take light sensitive proteins and we tether them to various different targets inside the cell. The target could be any protein. Which protein you choose depends on what do you want to achieve. So you can tune metabolism, you can activate growth factors, you can control transcription, you can control secretary capacity.
“The second part is hardware. So we build illuminators that are plug and play with existing bioreactor infrastructure. And then the third part is we have an AI algorithm that takes all of the sensor data, processes it, and makes predictions: What light pattern should I apply at this moment in time?
“We’ve built systems where you can do online measurements every second, feed all of that data back into the model, and the model can experiment with different light patterns… and this is all heading towards the first generation of truly driverless bioreactors, where you won’t need to have expensive humans adding expensive molecules into the bioreactors.
“You can just have a shared language between the bioreactors and the cells. And if you have that, then it simplifies the process dramatically.”
Therapeutic proteins an initial focus, but cultivated meat ‘still on the roadmap’
While Prolific Machines’ initial focus was on cultivated meat, it has since turned its attention to therapeutics, which presents more fertile ground in the short term, although Kent says he remains convinced that cultivated meat can and will happen.
“We grew meat with light, mainly as a proof of concept to show it was possible, because a lot of people didn’t believe it would be possible when I started this,” he said. “So it’s absolutely possible. We’ve made over 30 meatballs growing with light, with no growth factors.
“The reason our first application is therapeutic proteins is because they’re extremely expensive,” he added. “You can sell them for thousands of dollars per milligram and we found a niche in that space.”
As for cultivated meat, he said, “I still very much believe that cultured meat is an inevitability. It is going to happen, and I believe that Prolific’s technology is best suited to make it happen. The reason I started the company is because I wanted to end the exploitation of animals for food and for scientific research, and so it [cultivated meat] is very much still on our roadmap.
“The protein therapeutic work that we’re doing came first because there’s real low hanging fruit there, and we can become EBITDA positive quickly.”
