Era of personalized mRNA products driving demand for small-scale manufacturing. [Kateryna Kon/Science Photo Library/Getty Images]
RNA came to prominence during COVID-19 with mRNA vaccines saving millions of lives worldwide. Since then, the technology has evolved with some developers now focusing on personalized mRNA therapeutics rather than mass market products.
And this is increasing demand for small-scale manufacturing capacity, according to a California research and production contractor, Nutcracker Therapeutics.
“The CRDMO space for mRNA became crowded during the pandemic, but much of that production process was built for capacity and not flexibility. We’re now seeing a clear shift toward personalized mRNA therapies, especially in oncology.
“PCTs [personalized cancer therapies] and other patient-specific treatments are advancing through the clinic, and they require flexible, small-batch manufacturing, which is something traditional large-scale setups aren’t designed for,” a spokesperson told GEN.
Some notable examples of personalized mRNA products include Gritstone bio’s GRANITE and Moderna’s vaccine mRNA-4157, which are expected to enter the market in Q2 2027 and Q3 2030, respectively.
Small-scale manufacturing
For the contracting sector, the demand for small-scale production capacity is a real opportunity, according to Nutcracker, which says the latest iteration of its production platform—called NMU-Symphony—is designed to cater for this need.
The spokesperson said, “Today’s RNA manufacturing infrastructure is optimized for large batch sizes—thousands or even millions of doses—which presents a major hurdle when you need to produce just a handful of highly individualized therapies.
“Nutcracker developed the NMU platform to solve this very challenge: enabling RNA production to scale down efficiently, without compromising quality or speed.”
According to the firm, the platform’s key feature is a monitoring technology, called ProcessVision, that allows it to track synthesis in real time.
The spokesperson said, “Most RNA production today relies on external, post-process quality checks that add time and cost. In contrast, ProcessVision embeds over twenty real-time measurements directly into the platform via specially designed biochips.
“This real-time data allows us to release batches based on live parameters, reducing the burden of lengthy off-chip testing while still ensuring GMP-grade quality. It also helps eliminate variability between runs, which is a common issue when dealing with constructs unique to a single patient.”
As a result, Nutcracker claims it can manufacture a patient-specific dose of an mRNA therapeutic or vaccine within a three-week turnaround time.
“This is critical as the field shifts toward more ‘small-scale’ modalities, such as PCTs and in vivo gene editing for specific disease subtypes,” the spokesperson said.
The ability to make patient-specific products quickly fits with the needs of smaller, resource-limited developers, according to Nutcracker.
“These teams often need many different RNA sequences in small quantities, and legacy systems aren’t built for that level of flexibility. Our platform makes it feasible to move quickly and cost-effectively, whether you’re manufacturing personalized clinical doses or running preclinical lead optimization programs,” the spokesperson added.
