Context:

• This article is based on a news “Nobel Prize in Medicine 2023: Katalin Kariko and Drew Weissman for enabling development of mRNA vaccines” which was published in the Mint. The 2023 Nobel Prize in Medicine 2023 has been awarded to Katalin Karikó and Drew Weissman for their discoveries concerning nucleoside base modifications.

Nobel Prize in Medicine 2023

• The discoveries by the two Nobel Laureates were critical for developing effective mRNA vaccines against COVID-19 during the pandemic that began in early 2020. 

mRNA vaccines: A promising idea

• In our cells, genetic information encoded in DNA is transferred to messenger RNA (mRNA), which is used as a template for protein production. 
• RNA contains four bases, abbreviated A, U, G, and C, corresponding to A, T, G, and C in DNA, the letters of the genetic code(Refer image).
• During the 1980s, efficient methods for producing mRNA without cell culture ( in a lab ) were introduced, called in vitro transcription. 

• In vitro transcribed mRNA was considered unstable and challenging to deliver, requiring developing sophisticated carrier lipid systems to encapsulate the mRNA. Moreover, in vitro-produced mRNA gave rise to inflammatory reactions. 
• The duo showed that converting the RNA base uridine to pseudouridine in mRNA produced in vitro could reduce the inflammatory response.
• In subsequent years, mRNA vaccines were developed against Zika virus and MERS-CoV, but the technology was fully exploited only in 2020, during the Covid-19 pandemic.
• The mRNA vaccines from Moderna and Pfizer-BioNTech vaccines, with their nucleoside bases modified, were developed at record speed. 

Nucleoside base Modification:

• A nucleoside-modified messenger RNA (modRNA) is a synthetic messenger RNA (mRNA) in which some nucleosides are replaced by other naturally modified nucleosides or synthetic nucleosides (For Example uridine to pseudouridine). 
• modRNA (Modified RNA) is used to induce the production of a desired protein in certain cells. An important application is the development of mRNA vaccines, of which the first authorized were COVID-19 vaccines.
• Using modified nucleosides is a critical approach to mitigate the intrinsic immuno-response of exogenous mRNA and increase its translation for mRNA therapeutic applications. However, for vaccine applications, the intrinsic immunostimulatory nature of unmodified mRNA could help induce productive immunity. 
• Additionally, the ionizable lipid nanoparticles (LNPs) used to deliver mRNA vaccines can possess immunostimulatory properties that may influence the impact of nucleoside modification.

What approaches were adopted by the Indian vaccine manufacturers to produce COVID-19 vaccines?

mRNA and Other Vaccines

• All vaccines aim to induce an immune response by introducing the pathogen in advance. The critical difference is that most vaccine platforms inject either the virus (killed or inactivated) or a part of it. (Refer Image).
• In contrast, an mRNA vaccine delivers only the instructions, enabling the body to create the protein.
• Once the protein is synthesized, the immune system responds against it. The objective is for the body to recognize the virus’s protein if it infects the person in the future, and neutralize it. 

• In COVID-19 vaccines, the synthesized protein is Sars-CoV-2’s spike, responsible for latching on to and infecting a cell.
• DNA vaccines: which are often referred to as  third-generation vaccines, use engineered DNA to induce an immunologic response in the host against bacteria, parasites, viruses, and potentially cancer.
• The basic working principle behind any DNA vaccine involves using a DNA plasmid that encodes for a protein originating from the pathogen in which the vaccine will be targeted.

Also read: ICMR Study On Covid

Advantages and disadvantages of mRNA vaccines

Conclusion

Katalin Kariko and Drew Weissman, who together identified a chemical tweak to messenger RNA, thus both were awarded the Nobel Prize in Medicine for the year 2023. The advantages of the mRNA vaccine approach are numerous and, in addition to being used as a vaccine, mRNA can also be used as a protein supplement or replacement therapy to treat other diseases, driving the necessary research to overcome the current obstacles and limitations with the ultimate goal of developing an ideal form of medicine.

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