As RNA therapeutics evolve far beyond their vaccine origins, a new generation of scientists and manufacturers is rethinking how to produce these complex medicines safely, efficiently, and at scale. From template design and enzymatic capping to lipid nanoparticle (LNP) formulation and purification, the challenges extend across every stage of development. Four industry leaders—CordenPharma, GENEWIZ, Lonza, and New England Biolabs—are advancing the technologies, analytical methods, and supply chains needed to meet these demands. Together, their work reflects a shared mission: to turn RNA’s extraordinary biological potential into reliable and reproducible therapies for a wide range of diseases.
Commentary Excerpt by Lipids & LNPs Platform Directors Dr. Serra Gürcan and Dr. Jason Coleman
At CordenPharma, a global CDMO headquartered in Basel, Switzerland, scientists are expanding the frontiers of RNA-therapeutics manufacturing by refining the chemistry and engineering of LNPs to deliver RNA-based medicines. For CordenPharma’s Jason Coleman, PhD, Associate Platform Director for Lipids & LNPs, and Serra Gürcan, PhD, Platform Director for Lipids & LNPs, the goal is to help clients translate scientific innovation into scalable, high-quality production.
“In many ways, the manufacturing process itself is similar across applications,” Coleman explains. “The differences arise from the components in the formulation and how those components interact with the specific therapeutic application.” Both he and Gürcan bring deep experience in nanoparticle drug delivery, supporting customers through formulation, process development, and scale-up. “Our role today is to provide insight from the lipid-manufacturing standpoint—how to produce highly pure lipids, what to avoid, and how to maintain consistent quality across scales,” Gürcan says.
A lipid nanoparticle used as a delivery device for an RNA-based therapy includes several components: the RNA payload, helper lipid, sterol, stabilizer, and ionizable/cationic lipid. [CordenPharma]
CordenPharma’s expertise spans both the LNP process and the lipid inputs that define performance. The company supplies catalog lipids but also works closely with clients, developing novel, custom-designed lipids. As RNA therapeutics move beyond vaccines, these formulations are becoming more sophisticated. “LNPs are inherently complex,” Gürcan notes. “Now, with extra-hepatic delivery and conjugated LNPs, we’re adding more layers of complexity.” Beyond manufacturing, biological challenges persist—ensuring RNA escapes the cytosol, avoiding immunogenicity, and managing repeated dosing. Polyethylene glycol (PEG), for example, long used in the pharmaceutical industry to stabilize nanoparticles, has raised concerns. “Repeated dosing can reduce potency because the body begins to recognize PEG,” Gürcan explains. Coleman adds, “There’s a lot of work going on to develop PEG derivatives or find alternatives that avoid immune responses.”
Manufacturing conjugated or targeted LNPs introduces additional challenges. “Finding CDMOs that can produce conjugated LNPs at GMP scale is difficult,” Coleman says. To address this, CordenPharma is developing new conjugated lipids designed specifically for LNP chemistry and investing in expertise to perform bioconjugation at scale. The company also uses plant-based cholesterol derivatives that are less immunogenic and can increase RNA expression by up to 45%.
“Our innovation teams are focused on developing alternatives to PEG and expanding beyond mRNA to plasmid DNA and CRISPR-based payloads,” Gürcan says. Coleman adds that cost and consistency remain industry-wide priorities: “The real challenge isn’t just in manufacturing—it’s in improving delivery and doing it in a repeatable, reproducible, and affordable way. We’re not there yet, but we’re getting closer.”
Get in touch with our team of experts to explore bespoke end-to-end CDMO support of your complete drug lifecycle
at any scale.