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Team TFS
Team TFS

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As we have all been caught in the eye of the storm of the pandemic over the last 18 months, there is no getting away from it.  But simultaneously, there has been another storm brewing.  This one is more positive and in the center is messenger RNA, causing so many waves, that it is hailed as an mRNA revolution.

 

Key to success: stabilizing mRNA in the body


The molecule of ribonucleic acid (RNA) was discovered around 60 years ago as the critical intermediary between DNA, the genetic code and protein.  It was quickly realized that RNA could be synthesized and manipulated to tell the body what cells to produce.  The type of RNA called messenger RNA can be manipulated to act as a messenger service that instructs the body to produce certain proteins that can prevent, treat or cure disease.  However, no drug or therapy using this mechanism had ever made it to market.  The human body was too clever and quickly defended itself, destroying the synthetic RNA before it could reach its target. In some cases, it could actually become a health risk as the immune system went into overdrive.  Funding into synthetic RNA decreased, grants were turned down and the limelight no longer shone on this kind of therapy.

However, research did continue and key researchers such as Kariko and Weissman collaborated, experimented and tweaked, and kept on publishing.  By the early 2000s, mRNA was starting to get noticed again. As with all good scientific discoveries, there must be a lot of failures before success.  A hybrid mRNA was born, and the research continued in the background situated within small biotech companies and was mostly off the radar for large pharma.  Kairiko later became the Senior Vice President of BioNTech, continuing working with mRNA, mainly with candidates in oncology therapies.  That is . . . until 2020.

You would be hard-pressed to find a person on the planet not affected by the pandemic.  The need for a vaccine was dire and extremely urgent.  Without mRNA research bubbling away in the background and large pharma and governments to back and fund the research and manufacturing, it is doubtful this would have been the first vaccine to the market and the first-ever approved product using mRNA technology.  Moderna, another key player in mRNA, was able to design a vaccine within 48 hours of receiving the sequence, as did the National Institute of Allergy and Infectious Disease, without receiving any physical virus.  Truly revolutionary.

 

Where next for mRNA?


There are now two approved mRNA-based COVID-19 vaccines, and confidence in mRNA is riding high again, so where else can we apply this treatment?

Now that the mechanism of using mRNA in a way that it is cloaked from the immune system —  so it can carry out its correct function in the body —  is understood and more importantly proved, adapting the process for other viruses becomes relatively easy.

Moderna already has candidates ready for phase I trials for influenza, HIV and other respiratory viruses, plus a phase III candidate for cytomegalovirus (CMV), a mainly asymptomatic virus that’s linked to congenital birth defects.  Their mRNA pipeline also includes candidates for Zika virus, cancers and other rare diseases.  BioNTech also has a healthy pipeline in preclinical and phase I candidates.

One point to note is that collaboration on COVID-19 vaccines has been vital and this looks set to stay, as many companies who once competed now see the benefit to working together to find the next generation of prevention, treatment and cures of many diseases. This revolution is something we can all potentially benefit from as well as many generations to come.

 

Additional resources


Solutions page: Oligonuceotide therapeutic analysis

Press release: Collaboration with the University of Sheffield on Advanced Oligonucleotide characterization and adva...

On-demand webinar: Advancement of Analytical Technology for Oligonucleotide Analysis Using High-Resolution Accurate-Mas...

On-demand webinar: Automated workflow for mRNA sequencing by High Resolution LCMS