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Offering an existing library of proven chemistries and API synthetic routes.

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Messenger RNA: A Future in Modified Bases

The world of medicine is rapidly evolving. New therapeutics and vaccines are constantly being discovered based on novel mechanisms of action. The modified base mRNA market represents an emerging, high-growth market opportunity, and Bright Path Labs can play a substantial role in this emerging market via manufacturing and scaling modified bases, a key component needed for the cellular delivery of mRNA vaccines and therapeutics. To understand Bright Path Labs role in this market, it is important to understand the MOA of mRNA vaccines and therapeutics.

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Fundamentals

Within the nucleus of every cell are blueprints (i.e., DNA) for constructing life. DNA produces mRNA through a process called transcription, and the mRNA produces proteins through a process called translation.

Innovation

In the 1990s, Katalin Karikó, a researcher at the University of Pennsylvania believed mRNA could create “antibodies to vaccinate against infection, enzymes to reverse a rare disease, or growth agents to mend damaged heart tissue.” The problem she ran into is that the body’s immune system would destroy the foreign mRNA strand before it could produce the desired protein.

Modified Bases

Karikó and a colleague, Dr. Drew Weissman, found the solution, which they subsequently published in 2005. To understand the solution, it is important to understand the structure of mRNA.

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mRNA is made of nucleotides, which can be divided into three components:

  • Phosphate group(s)

  • Ribose sugar

  • Nitrogenous base
     

Blue rectangle = nucleotide =
sugar + nitrogenous base + phosphate group(s)

Green rectangle = nucleoside = sugar + nitrogenous base

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COVID-19

In the context of fighting an infection like COVID- 19, synthetically modified mRNA vaccines like that of Pfizer and Moderna code for the signature “spike protein.” The “spike protein” does not induce sickness in the individual given that the protein is not the sickness inducing part of the virus. The protein activates the immune system to produce cells that would help destroy the virus if one were to be infected with the pathogen.

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The Importance of Synthetically Modified mRNA

Despite being revolutionary, the importance of synthetically modified mRNA remained under the radar for years. However, in 2010, it caught the attention of Robert Langer, the most cited engineer in the world with over 1400 patents. He remarked that starting a company focused on synthetically modified mRNA “could be the most successful company in history.” He along with three other colleagues founded Moderna, whose R&D would be focused on modified mRNA’s potential. To give an early introduction into the market potential of synthetically modified mRNA, Moderna had over $1.8 billion USD of funding by 2018 before they even had a single drug to market. More recently, Moderna has become well known after putting its first drug out of the clinical development pipeline, which is a synthetically modified mRNA COVID-19 vaccine.

Within the last decade, mRNA’s versatility as both a vaccine and therapeutic has become more widely recognized. “The use of mRNA has several beneficial features over subunit, killed and live attenuated virus, as well as DNA-based vaccines,” such as safety, inexpensive manufacturing & scaling, stability, and versatility. What makes mRNA an effective therapeutic is that it can be used to code for the synthesis of proteins, which has several applications for clinical intervention. As one example, it can be used to produce proteins specific to one’s malignant tumor that tells the body to kill any circulating tumor DNA. mRNA’s versatility is why CureVac’s cofounder, Dr. Ingmar Hoerr, remarked “mRNA drugs have the potential to fill critical gaps not met by traditional small molecule drugs, available biological treatments and emerging gene therapeutics."

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