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Content

• Introduction
• Background
• Contributions
• Development of Vaccines

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Introduction

The 2023 Nobel Prize in Physiology or Medicine has been awarded to Katalin Kariko (Hungary) and Drew Weissman (USA) for their discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccine against COVID-19. Through their groundbreaking findings, which have fundamentally changed our understanding of how mRNA interacts with our immune system, the laureates contributed to the unprecedented rate of vaccine development during the COVID-19 crisis.

Background:

• Other methods of vaccine development – Whole Virus -, protein-, and vector- based vaccines requires large scale cell culture. It is a resource intensive process and limits the possibilities for rapid vaccine production in response to outbreaks and pandemics. mRNA based vaccines solved these problems.

During the 1980s, efficient methods of producing mRNA without cell culture were introduced, called in-vitro transcription. Ideas of using mRNA technologies for vaccine and therapeutic purposes also took off, but roadblocks lay ahead.

• In vitro transcribed mRNA was considered unstable and challenging to deliver. It required development of sophisticated carrier lipid systems to encapsulate the mRNA.
• This mRNA also gave rise to inflammatory reactions.
• These problems limited the enthusiasm for developing the mRNA technology for clinical purposes.

Contributions:

• In 1990s, Kariko was an assistant professor at the University of Pennsylvania and met immunologist Drew Weissman there.
• They worked together to prevent the immune system from launching an inflammatory reaction against lab-made mRNA, previously seen as a major hurdle against therapeutic use of mRNA.
  • They found that inflammatory response was almost abolished when base modification was included in the mRNA. Therefore, in 2015 they published that adjustments (modifications) to nucleosides, can keep the mRNA under the immune system’s radar.
  • Later, they also showed that the delivery of mRNA generated with base modification markedly increased protein production compared to unmodified mRNA. This effect was due to the reduced activation of an enzyme that regulates protein production.

Development of Vaccines:

• After the above discoveries, interest in mRNA technology picked up. Vaccines for Zika and MERS-CoV were pursued.
• After the outbreak of COVID-19 pandemic, two base modified mRNA vaccines encoding the SARS-CoV-2 surface protein were developed at record speed. Protective effects of around 95% were reported, and both vaccines were approved as early as Dec 2020.
• The impressive flexibility and speed with which mRNA vaccines can be developed pave the way for using the new platform also for vaccine against other infectious diseases.
• In the future, the technology may also be used to deliver therapeutic proteins and treat some
  cancer types.

How mRNA vaccine protects you against COVID-19:

• Through their fundamental discoveries of the importance of base modification in mRNA, this year’s Nobel Laureates critically contributed to this transformative development during one of the biggest health crises of our time.