From not likely to Nobel Prize: mRNA’s rise to fame

For years the modality was deemed unfeasible but COVID-19 kickstarted a vaccine revolution and the pioneers have been awarded this year’s Nobel Prize for Medicine.  

Biochemist Katalin Karikó, and immunologist Drew Weissman have been awarded the Nobel Prize for Medicine for their discoveries concerning nucleoside base modifications that supported the development of messenger RNA (mRNA) vaccines against COVID-19.

Together, at the University of Pennsylvania (UPenn), the pair focused on how different RNA types interact with the immune system. In turn, Karikó and Weissman identified that dendritic cells recognize in vitro transcribed mRNA as unfamiliar but mRNA from mammalian cells did not provide the same reaction. This led the co-winners to realize some critical properties must determine the different types of mRNA.

Katalin Karikó, this year’s co-winner of the Nobel prize for Medicine. Image c/o Nobel Prize

From this initial breakthrough, industry tentatively embraced the modality, yet it was the pandemic that validated the concept.

The word ‘mRNA’ only entered the layman’s non-scientific conversation in the past three or so years as Moderna and BioNTech/Pfizer released their successful and respective COVID-19 vaccines.

Massachusetts-based firm Moderna Therapeutics, best known for its breakthrough cell-free COVID-19 vaccine, mRNA-1273, began its journey in 2010 as ModeRNA (a combination of modified mRNA) and invested heavily in the modality across several years.

Along with the success of BioNTech/Pfizer’s COVID-19 vaccine, which received emergency use approval in December 2020, Moderna has assisted in validating the concept of mRNA technology. In turn, multiple companies have invested in mRNA as the risk is no longer so large, and the concept is most definitely real.

Firms across the globe began to bolster their mRNA capabilities relatively quickly after the modality received validation. Sanofi acquired Translate Bio in August 2021 for a total equity value of approximately $3.2 billion as the French pharma giant built on its plans to invest €400 million ($475 million) annually into what it describes as its ‘mRNA Center of Excellence’ to accelerate R&D of next-generation vaccines.

In the same month, Seqirus, known in the influenza space through its portfolio of products, including both egg-based and cell-based vaccines, stepped up its efforts to develop a flu vaccine based on mRNA.

Drew Weissman, this year’s co-winner of the Nobel Prize for Medicine. Image c/o Nobel Prize

Additionally, Ginkgo Bioworks claimed its partnership with Aldevron (formed earlier in 2021) had led to an mRNA breakthrough with their manufacturing approach proving 10 times more efficient than the previous process.

Two years on, investment in the modality, its technology, and partnerships has not stopped.

Collaborations

This month, Ginkgo inked an RNA deal with Pfizer worth a potential $331 million. Last month, vaccine firm Tianjin CanSino Biologics extended its research alliance to provide contract development and manufacturing services for AstraZeneca’s mRNA vaccine program.

And in May, ReciBioPharm (previously Arranta Bio) partnered with Massachusetts Institute of Technology (MIT) to develop a continuous manufacturing technology for mRNA therapeutics as part of the US Food and Drugs Administration’s (FDA’s) initiative to create a fully integrated, continuous production line for mRNA vaccines, which will support future pandemic threats.

Funding

With such large volumes of funding and specific programs and financing supported by different governments, it is clear mRNA is here to stay.

In August, the Japanese government announced it would pay $115 million in two separate grants to mRNA contract development manufacturing organization (CDMO) Arcalis. The funding will be used to finance the construction of a facility in Minamisoma City, Japan, as well as buying the relevant equipment needed for mRNA drug substance manufacturing and operations.

One month before, MIT received $82 million in FDA funding to conduct a three-year research program to design a fully integrated continuous mRNA platform. And in June, WestGene Biopharma, a two-year old mRNA company, completed a $42 million funding round to advance its portfolio of tumor treatment vaccines in China and global trials.