Although largely in the background until recently, Prolific Machines’ optogenetic approach to biomanufacturing is about to make a splash with the company achieving an impressive milestone in monoclonal antibody (mAb) production.
Now, in addition to a recent new technology designation from the FDA and increased interest in its platform from industry heavyweights, Prolific is increasingly well-positioned as its light-controlled production methods come into the spotlight.
Prolific announced that it has reached a record-breaking productivity milestone of 21 g/L in a 15-day enriched fed-batch Chinese hamster ovary (CHO) cell line run of mAbs, leveraging a custom-built Photomolecular platform designed to “directly and dynamically” manipulate gene expression in living cells using light and optogenetics.
According to an April 5 press release, this is significantly higher than the industry standard of less than 10 g/L, which Prolific estimates puts it on track to meet its fed-batch manufacturing yield target of 25 g/L by the end of the year.
Prolific CEO and co-founder Dr. Deniz Kent said his company wants to spread this technology across the biopharmaceutical ecosystem. The company believes its approach has the potential to revolutionize traditional biomanufacturing methods by giving developers “precise, real-time control over when and how much protein cells produce,” according to a statement.
In contrast, today’s cells are primarily controlled by genetic systems that are “always on,” meaning molecular approaches that “once you add them, you can’t remove them, and you can’t dynamically change them,” Kent explained in a recent interview with Fierce.
According to the company, Prolific’s luminescent approach not only increases the efficiency of monoclonal antibody production, but also has the potential to address important developability and low-yield challenges that potentially threaten the commercial viability of next-generation complex biologics.
Apart from the magnitude of Prolific’s yields, the company noted that its platform’s mAb runs maintain approximately 87% viability at harvest, with a peak viable cell density of 33 million cells/mL. Additionally, a specific productivity of approximately 60 pg/cell/day was maintained in this experiment.
In essence, Prolific’s platform is a toolkit that combines synthetic biology, hardware and software to allow light to selectively control processes within cells, Kent said.
“Our technology is basically like this Rosetta Stone that converts digital inputs like electricity and light into biological inputs that are biochemical cascades,” Kent explained.
His company’s long-term goal is to build a “translation layer” between machines and cells, allowing AI algorithms to control cells in biomanufacturing.
Currently, Prolific is “using one color of light to control one process, transfer,” Kent said, adding that “the ultimate goal is to control multiple different processes with multiple different colors of light.”
At that point, Kent estimates Prolific will reach its “productivity limit,” which he estimates could be around 40 or 50 grams per liter.
Prolific’s approach revolves around light-sensitive proteins, the lighting system that Prolific uses to activate specific metabolic pathways, and the company’s AI-powered smart control system designed to monitor and adjust lighting in real time.
Kent explained that the hardware portion of the platform is “plug and play” with a company’s existing infrastructure. “We just sent a team of engineers, they installed some lighting equipment in the existing bioreactor, and suddenly the yield tripled,” he said.
In short, “we’re building the world’s first unmanned bioreactor,” Kent added. “Intelligent machines can now use light to control biomanufacturing for the first time.”
Kent believes that Prolific’s platform could offer even greater opportunities beyond monoclonal antibodies for more complex molecules such as multispecific molecules, cytokines, and fusion proteins.
As for how Prolific aims to leverage its platform in the commercial realm, Kent said, “We want to make this accessible to everyone in the ecosystem,” adding, “We don’t want this to be just for us.”
Although Prolific cannot discuss specifics at this time, Kent said its platform has already attracted attention from major CDMOs and branded pharmaceutical companies alike.
Founded in the Bay Area in 2020, Prolific was able to secure a $55 million Series B funding round in mid-2024, led by Ki Tua Fund, with support from Breakthrough Energy Ventures, Mayfield, SOSV, Shorewind Capital, Darco Capital and others.
Meanwhile, in another sign of the company’s growing profile, Prolific was added to the FDA’s Emerging Technologies Program under the Center for Drug Evaluation and Research last May. Through collaboration with authorities, this program is designed to help facilitate the regulatory process for developers of innovative manufacturing approaches.
