mRNA capping is a specific technology that a majority of mRNA vaccines have that is little known or discussed, outside of vaccine development. This technology is utilized in 75% of all approved mRNA COVID vaccines.
mRNA capping is a specialized structure placed in the beginning of the mRNA molecule, acting like a protective shield, and enabling it to generate the desired therapeutic effect.1 It helps in the delivery and efficacy of vaccines.
“One of the downsides to mRNA is the fact that it’s really not the most stable molecule, but there are things that you can do in the design of that molecule to really enhance its stability, to really make it a more effective molecule, just through the design of the molecule itself. And that’s really where mRNA capping comes into. So if you can envision the mRNA molecule a little bit like a car, then you can think of the mRNA cap as the front bumper on the front of the car. And that’s really there to protect the car or the molecule itself; in this case, from being broken down or being degraded,” said Kate Broderick, PhD, chief innovation officer, Maravai LifeSciences in an interview with Contagion. She says another role the capping provides is to serve as a GPS. “The cap also helps position the molecule when it needs to be in the cell.”
This is an image of mature mRNA. “Capping at their 5’ end acts as a defensive shield, safeguarding the mRNA molecule from premature breakdown. This ensures the message reaches its intended destination – the ribosomes, cellular machinery responsible for protein production. Without proper capping, the mRNA would degrade rapidly, rendering its intended purpose as a vaccine or therapeutic useless,” TriLink writes.1
Image Credit: NIH/TriLink Biotechnologies
TriLink Biotechnologies is a subsidiary of Maravai and is looking to improve the mRNA capping platform. One of its signature products is titled the CleanCap, and the technology offers a 5-inch cap structure that is integral to the stability, expression, and immunogenicity of an mRNA product. According to the company, the technology offers: 1-pot co-transcriptional capping strategy; mRNA with an optimal Cap 1 structure; and over 95% capping efficiency. Additionally, co-transcriptional capping with this technology overcomes the limitations of legacy capping methods.
Broderick was part of teams that helped to create successful vaccines for Ebola, Zika, Lassa fever, and MERS before tackling COVID-19. In early 2020, she was invited to take part in the first emergency meeting of the World Health Organization (WHO) about what was then called the novel coronavirus. Broderick was part of a small group of scientists from around the world to go to Geneva, Switzerland for a 2-day meeting. “At that point in time, it was February 2020, so it was all still very much China-focused at that time, but it was really to better understand the virus as we knew it at that time, and really take that back to our respective countries, and how we might apply that to coming up with new vaccine designs, and how we could apply that to better preparing our countries for the potential of the pandemic,” Broderick said.
This year, Broderick was named one of the Top 25 Biotech Executives of 2024 for the Healthcare Technology Report.
Broderick spoke to Contagion about the exciting aspects of the capping platform, mRNA technologies, and what the field is working on to deliver targeted vaccines and therapies.
