mRNA
1. Context
COVID-19 became the first-ever pandemic during which a vaccine could be quickly developed and deployed to prevent infections and deaths. Never-before-approved mRNA vaccines were used on humans and worked. The first two vaccines to be approved and deployed with this technology were rolled out by Pfizer and Moderna within a year. However, developing these vaccines would not have been possible without Katalin Karikó and Drew Weissman, whose breakthrough research laid the template in 2005 and ensured that mRNA vaccines were safe and did not lead to excessive inflammatory immune response. Both are winners of the Nobel Prize in Medicine or Physiology, 2023
2. What is mRNA?
Messenger RNA (mRNA) is a type of genetic material that plays a crucial role in the process of protein synthesis within cells.
It serves as an intermediary between DNA and proteins in the cell, carrying the genetic instructions needed to build proteins from the cell's nucleus to the ribosomes in the cytoplasm, where protein synthesis occurs
Key features and functions of mRNA:
- mRNA carries genetic information from the DNA in the cell's nucleus to the ribosomes, which are the cellular machinery responsible for assembling proteins
- The process of creating mRNA from a DNA template is called transcription. During transcription, a specific segment of DNA is used as a template to synthesize a complementary mRNA strand.
- The mRNA strand is synthesized in such a way that it represents a copy of the genetic information encoded in the DNA, with thymine (T) in DNA being replaced by uracil (U) in mRNA
- mRNA consists of a series of nucleotide triplets called codons. Each codon corresponds to a specific amino acid or serves as a start or stop signal for protein synthesis.
- There are 64 possible codons, each specifying one of the 20 different amino acids used in protein synthesis
- Once mRNA is synthesized, it exits the nucleus and moves to the cytoplasm, where ribosomes read the codons on the mRNA strand to assemble amino acids in the correct order, forming a polypeptide chain. This chain eventually folds into a functional protein.
- mRNA is relatively short-lived within the cell. It is synthesized when needed for protein production and is then rapidly degraded once its role in protein synthesis is complete.
- mRNA sequences can vary among individuals and among cells within an individual. This variability allows cells to produce specific proteins in response to various signals and environmental conditions.
3.mRNA Vaccine
mRNA vaccines are a groundbreaking type of vaccine that use synthetic messenger RNA (mRNA) to trigger an immune response in the body. Unlike traditional vaccines, which often contain weakened or inactivated forms of the pathogen (such as a virus) or pieces of it (such as proteins), mRNA vaccines do not contain the pathogen itself.
Instead, they provide the body with the genetic instructions (mRNA) needed to produce a harmless piece of the pathogen, typically a protein, which then stimulates an immune response
The first mRNA vaccine to receive emergency use authorization (EUA) and widespread use was the Pfizer-BioNTech COVID-19 vaccine. It was co-developed by the American pharmaceutical company Pfizer and the German biotechnology company BioNTech. The vaccine is known as BNT162b2 or Comirnaty
3.1.Function of mRNA vaccine
- The function of an mRNA vaccine is to stimulate an immune response in the body against a specific pathogen, such as a virus, by introducing a small piece of synthetic messenger RNA (mRNA) that encodes a harmless piece of the pathogen's protein
- Scientists design and synthesize a short piece of mRNA in the laboratory. This synthetic mRNA contains the genetic instructions for producing a specific protein that is found on the surface of the target pathogen
- To protect the fragile mRNA and facilitate its entry into human cells, the synthetic mRNA is encapsulated in lipid nanoparticles. These lipid nanoparticles serve as delivery vehicles for the mRNA
- The mRNA vaccine is administered to the recipient through a standard intramuscular injection, usually into the upper arm
- The lipid nanoparticles containing the synthetic mRNA are taken up by host cells at the injection site
- Once inside the host cells, the synthetic mRNA is recognized by the cell's protein synthesis machinery, including ribosomes.
- The ribosomes read the mRNA sequence and start producing the specific protein encoded by the mRNA.
- In the case of mRNA vaccines, this protein is a piece of the pathogen (e.g., a part of the spike protein of the virus).
- The newly produced viral protein is displayed on the surface of the host cells. This protein is harmless and cannot cause the disease itself, but it serves as a marker for the immune system.
- The immune system of the recipient recognizes the displayed viral protein as foreign and potentially harmful. This recognition triggers a robust immune response, including the production of antibodies specific to the viral protein
4. Why does mRNA make great Medicine?
- Though mRNA has existed in our biological makeup for some time, it took extensive research spanning decades for scientists to grasp how cells identify and utilize mRNA in protein synthesis. Eventually, it became evident that mRNA held significant potential as a formidable medical tool.
- Understanding how mRNAs encode proteins enables scientists to craft protein blueprints effortlessly. These blueprints can be adjusted to suit a patient's requirements, whether by creating entirely new mRNA recipes or tweaking existing ones for slight protein variations.
- The scalability of producing mRNA treatments lies in the capacity of scientists to generate substantial quantities of mRNA in laboratory settings.
- Unlike conventional drugs, where each compound possesses unique chemistry requiring distinct manufacturing techniques, the process to create one mRNA remains consistent across all types. It’s akin to mastering a basic risotto recipe, allowing for endless variations once the fundamentals are understood.
- An advantage of using mRNAs as medicinal agents is the innate ability of cells to degrade them when they're no longer necessary.
- Given their impermanence, adjusting doses to accommodate changing patient needs is easily achievable. Many diseases stem from cells producing incorrect proteins, mutant protein versions, or insufficient normal protein levels.
- By delivering corrected mRNA blueprints to affected cells, scientists can facilitate the production of the proper proteins.
- Exploration into mRNA's therapeutic potential spans various ailments like heart disease, neurodegenerative conditions, bone loss, and more. While most studies remain in early developmental stages, they hold promise for future treatments utilizing mRNA in protein replacement therapies.
- For instance, one mRNA medication stimulates new blood vessel formation, aiding in the healing of wounds in diabetic patients with poor circulation and heightened amputation risks. Another example involves using mRNAs to address propionic acidaemia, a condition where children have low levels of two liver proteins crucial in preventing the accumulation of harmful by-products in the body.
- The ability to tailor and produce mRNA easily amplifies their potential as effective, personalized therapies with fewer side effects, offering substantial aid to many individuals
5.Challenges to mRNA technology
- While mRNA (messenger RNA) technology has shown great promise, especially in the development of COVID-19 vaccines, it is not without its challenges and limitations
- mRNA molecules are inherently fragile and can degrade easily. This necessitates stringent storage and transportation requirements at very low temperatures for some mRNA vaccines, like the Pfizer-BioNTech and Moderna COVID-19 vaccines.
- Maintaining the "cold chain" can be logistically challenging, especially in regions with limited infrastructure.
- The production of mRNA vaccines, particularly for novel vaccines, can be costly. This cost can impact access to these vaccines, especially in lower-income countries
- mRNA vaccines typically have a shorter shelf-life compared to some other types of vaccines. This can pose challenges in terms of distribution and administration, particularly in regions with limited healthcare infrastructure
6. Way forward
The potential for mRNA-based medicine extends beyond vaccines to prevent infectious diseases. One example is the use of mRNA to treat cancer.
Some mRNA cancer treatments work like vaccines by training your immune system to specifically target cancer cells. As cancer cells grow, they rapidly gain mutations in many genes. Cancer vaccines contain mRNA recipes based on mutations commonly found in certain types of tumours. When injected into the body, the mRNAs from the vaccines allow normal cells to make those mutated proteins and broadcast them to the immune system, ramping up production of antibodies. These antibodies bind to cancer cells and mark them for immune attack
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For Prelims: Current events of national and international importance.
For Mains: General Studies III: Science and Technology- developments and their applications and effects in everyday life
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Previous Year Questions
1.In the context of vaccines manufactured to prevent COVID-19 pandemic,
consider the following statements : (UPSC CSE 2022)
1. The Serum Institute of India produced COVID-19 vaccine named Covishield using mRNA platform.
2. Sputnik V vaccine is manufactured using vector based platform.
3. COVAXIN is an inactivated pathogen based vaccine.
Which of the statements given above are correct ?
A. 1 and 2 only
B. 2 and 3 only
C. 1 and 3 only
D. 1, 2 and 3
Answer (B)
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Source: indianexpress
