Addressing Challenges in mRNA and LNP Manufacturing (Part One)

Two of the challenges that Nutcracker Therapeutics, a US-based RNA medicines company, has been working through are how to approach the manufacturing of RNA-based drugs for personalized therapies and how to bridge the gap between smaller-scale companies and clinical trial-scale studies, says Colin McKinlay, senior director, Chemistry and Delivery Technologies, Nutcracker Therapeutics.

“I think one of the lessons learned from the whole COVID[-19] pandemic and putting together the mRNA [messenger RNA]-based vaccines for COVID[-19] was that we could actually scale these up to … worldwide scales, and that we were able to do that fairly effectively. But starting to think about distributing and manufacturing mRNA drugs, where every patient has a different type of formulation, I think that starts to be a different type of challenge,” McKinlay says.

“[A]nother area that has [many] challenges associated with it is really being able to bridge smaller-scale companies … bridge their research work into Phase I, Phase II clinical-trial scale and get them materials that they need for conducting those trials,” he adds, noting that while there are many commercial suppliers available for research-grade mRNA and making mRNA at that small scale for drug discovery work, the cost for scaling up to larger-scale commercial manufacturing can be prohibitive. Therefore, there is need in the market for enabling small startups to scale up manufacturing, for both mRNA and lipid nanoparticles (LNPs).

“[Many] of the commercial options for making LNPs aren't really tailored towards … small scale. There [are] systems that are available from various … suppliers, but they generally have a pretty large minimum volume or minimum scale that they can operate at. So, what [many] people end up doing is resulting to just pipette-mixing or hand-mixing their components, which means that the LNPs [being made] are very different than the LNPs that [are] going to be [made] farther down in [the] development process and in … scale up,” McKinlay explains.

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About the speaker

Colin McKinlay, PhD, Senior Director, Chemistry and Delivery Technologies, Nutcracker Therapeutics

Colin McKinlay is the senior director of Chemistry and Delivery Technologies at Nutcracker Therapeutics. He has more than 10 years of expertise in nucleic acid delivery through his current position at Nutcracker Therapeutics and his doctoral research at Stanford University with Professors Paul Wender and Robert Waymouth. This research involved preparation of synthetic delivery vehicles through organocatalytic ring-opening polymerization, and their characterization and in-vitro and in-vivo evaluation for the delivery of DNA, RNA, and other biological macromolecules. He holds over five patents and nine peer-reviewed publications on chemical delivery technologies. McKinlay has led the delivery efforts at Nutcracker Therapeutics since 2018, including the establishment of its unique peptoid-based Nutshell delivery platform.