Where is mRNA Headed Now?

January 17, 2024 by Mark Wetzel

Looking for the next steps ahead

The trajectory of the mRNA modality is set to keep rising as we learn more about its applications and where we are headed in the field. I recounted in my observations from the International mRNA Health Conference, held in Berlin, Germany, we are moving beyond the beginning, with numerous paths forward for mRNA usage.

It’s gratifying to see scientific developments in the field, with approaches related to bacterial/viral vaccines, translational medicine, novel delivery systems, cancer vaccines, genetic diseases, and tissue-specific targeting. This continued emergence of mRNA therapeutics as an independent field, displaying its significant potential to address variety of human diseases and beyond is an exciting thing.

During our discussions at the Berlin conference, it became clear the mRNA field has made significant advances over the past year. Academic and industry groups have programs operating to expand the use of mRNA to other human diseases, as well as the broader areas dealing with community health and food safety.

Intriguing developments
Some of these programs are designed to address acute and chronic human conditions and require the development of advanced technologies for lowering immunogenicity from systemic administration of mRNA-LNPs, enhancing targeted delivery. Additionally, developing built-in mechanisms in the mRNA’s primary sequence for tissue-specific expression or incorporating mRNA sequence elements can enhance translation and stability.

To this end, several groups are working on development of complex arrays of ionizable lipid, while demonstrating their use in robust control of encapsulation of nucleic acids (mRNA, plasmid DNA, oligonucleotides, siRNA and miRNA), accompanied by strong tissue targeting abilities and enhanced cellular expression/response.

One interesting way to generate nanoparticles is generating EABR nanoparticles by utilizing ESCRT machinery to create what is called hybrid vaccines – mRNA and protein hybrid vaccines. The “hybrid” definition is because mRNA encapsulated in LNP is first introduced into HEK293 cells for mRNA translation. The protein product of this mRNA is then assembled in HEK293 cells to create 50nm defined sized nanoparticles using the ESCRT machinery, which is purified and introduced as drug product.

Another item of interest in the expanding mRNA therapeutics space is its diverse application in veterinary medicine for highly contagious bacterial diseases in cattle, and to control tick and mosquito borne diseases by halting the transmission cycle.

From the industry side, Contract Development and Manufacturing Organizations (CDMOs), Contract Testing Labs (CTLs) and Contract Research Labs (CRLs) involved in manufacturing, developing, and testing mRNA and LNPs, presented overviews of their technologies. These highlighted the importance of developing next-generation analytical methods for drug substances and drug products, to match the developing advanced technologies and complexities of the growing mRNA therapeutics space.

From the potential to target solid tumors, which are the most difficult to treat, by “tricking” tumor and immune cells, to using mRNA in conjunction with other modalities, we are seeing a great change from just even a year ago in applications and opportunities. In this next year, I look forward to even more change and advances that we can share.

• Learn more about Aldevron’s mRNA platform and services
• Have questions on this topic? Contact Mark Wetzel
• Visit the Alliance for mRNA Medicines (AMM) website
• Have an idea for a topic? Let us know!

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