mRNA technology: When it comes to the COVID-19 vaccine, mRNA is in the limelight these days. Even though it’s a new concept, it’s attracting considerable interest.
The swift formation of the first licenced mRNA vaccines was prompted by the COVID-19 pandemic and when the causal virus SARS-CoV-2 began at the start of 2020.
One of the reasons for its notoriety is that it uses a different strategy for treating illnesses than any other pharmaceutical category.
One unique feature of mRNA is that it uses normal biological processes to specify proteins and has a therapeutic impact.
This opens the door to the treatment of a variety of ailments that were previously thought to be incurable. Without a doubt, mRNA has the potential to change how drugs are discovered.
This invention is significant in the medical field since no such drug has ever been produced and made effective to this degree and scale.
What is mRNA, exactly?
When a single RNA molecule becomes analogous to one of the DNA strands of a gene, the produced single stranded RNA is called mRNA or Messenger RNA.
However, there isn’t much of a distinction between RNA and mRNA. The mRNA is similar to an RNA that has left the cell nucleus of the gene and has moved to the cytoplasm which is the production house of the proteins.
It is very interesting to note that when a protein synthesis is taking place, an organelle known as ribosome paces alongside the mRNA to read its primary sequence, which later on it uses this very genetic code to make sense of each of the three base triplet, also known as Codon into its associated amino acid.
The SARS-CoV-2 virus, which causes coronavirus sickness, is not included in the vaccine, nor are any portions of it. The vaccine instead contains transmitter RNA, which tells the body to make coronavirus surface protein, also known as spike protein.
Water, salts, carbohydrates, and lipids are also included in the vaccination. The mRNA in the vaccine is enclosed in a small lipid particle that aids in its delivery to a muscle cell.
The Early Evidence of mRNA
In 1989, researchers disclosed the first successful transmission of customised mRNA encapsulated within a liposomal nanoparticle into a cell. A year later, untreated lab-made mRNA was delivered into the musculature of mice.
These experiments were among the first to show that in vitro synthesis mRNA with a specific gene could transmit the genetic information needed to make a particular protein within living cell tissue, paving the way for messenger RNA vaccines to be proposed.
T lymphocytes in mice were stimulated by liposome-encapsulated mRNA expressing a viral antigen in 1993. Self-amplifying mRNA was created the next year by combining a viral antigen with a replicase encoding gene.
A viral infection was employed to generate both a cellular and humoral immune response in mice using this approach.
The next year, it was shown that mRNA encoding a tumour antigen elicited a comparable immune response against cancer cells in mice.
What do mRNA do?
The main function of mRNA is particularly to produce the instructions in order to produce protein that may treat and prevent diseases.
The molecules of mRNA are not small molecules just like traditional pharmaceuticals nor are they treated as traditional biologics which is the main basis of the biotech industry.
The mRNA are collections of instructions that direct the cells of the body to produce protein in order to prevent or fight from the disease.
The concept of mRNA is rather just a basic human biology where a DNA, that is defined as a double stranded molecule which stores the genetic instructions of the cell in our body and which instructs them to make protein.
Protein is said to be the “workhorses” of our body as nearly each and every bodily function, whether normal or disease related, is carried out with the help of one or many proteins.
When a person is vaccinated by the mRNA, it delivers a short lived synthetically generated RNA sequence of a virus into that person. The process of phagocytosis helps to generate the mRNA fragment with the help of dendritic cells.
Dendritic cells read the mRNA and make the viral antigens that the mRNA encodes using their own machinery (ribosomes). After some days of introducing the vaccination in the person’s body, the mRNA fragments start to get degraded.
The special feature of the Dendritic cells is that it takes the vaccine mRNA globules far more quickly than non-immune cells, which can also absorb vaccine mRNA, generate antigens, and show antigens on their surfaces.
With the above explanation, we can say that mRNA is as important as DNA as without mRNA our body would have never used our genetic code, there would have been no production of protein, and our body would have never performed the functions as easily as it is currently.
Types and functions of RNA
Among all the types of RNA, mRNA that is messenger RNA, tRNA that is transfer RNA, and rRNA that is ribosomal RNA are the most renowned.
All the three of them are said to be present in all the organisms. The biochemical reactions that occur in these and other types of RNAs are similar to enzymes. Some are said to have even more complex regulatory functions in cells.
Because of their involvement in many regulatory processes, their abundance, and the diverse function they possess, RNA plays a crucial role in normal cellular processes and diseases.
Connection between RNA and disease
A strong connection between RNA and human illnesses has been uncovered. As mentioned previously, some particular miRNAs have the ability to alter cancer-related genes in ways that help to cure tumour formation. Dysregulation of miRNA metabolism, however, has been known to cause a number of neurological illnesses such as Alzheimer’s disease.
When it comes to other RNA types, such as tRNAs, it can attach to caspases, which are special types of proteins known in apoptosis.
tRNAs are said to block apoptosis by binding it to caspase proteins; the capacity of these cells to enter the programmed death signals is one of the major characteristics of cancer. tRNA-derived fragments are basically noncoding RNAs that are also thought to play a major role in cancer.
An increased levels of MALAT1 have been detected in numerous malignant tissues and are connected with the proliferation and metastasis (spread) of tumour cells, especially with the development of technologies like RNA sequencing.
RNA-binding proteins (RBPs) are known to be confined by a class of RNAs with repeat sequences, leading in the development of foci or aggregation in neural tissues.
Neurological illnesses like amyotrophic lateral sclerosis (ALS) and myotonic dystrophy are caused by these aggregates. RBP dysfunction, dysregulation, and mutation have all been linked to a variety of human disorders.
Additional relationships between RNA and illness are anticipated to be discovered. Such findings are expected to be aided by a better knowledge of RNA and its activities, as well as the continuous development of sequencing technology and attempts to screen RNA and RBPs as therapeutic targets.
Advantages of mRNA
In comparison to regular immunizations, mRNA vaccines provide a number of benefits. mRNA vaccines are non-infectious since they are not made from an active pathogen (or even an inactivated disease).
Traditional vaccinations, on the other hand, necessitate the creation of pathogens, which, if done in large quantities, might raise the danger of localised viral outbreaks at the manufacturing plant.
Another benefit of mRNA vaccines is that, because the antigens are synthesised inside the cell, they induce both cellular and humoral immunity.
mRNA vaccines have the benefit of being able to be created quickly. In just two days, Moderna created the COVID-19 mRNA-1273 vaccine.
They can also be produced more quickly, more cheaply, and in a more uniform manner, which helps increase responsiveness to serious outbreaks.
mRNA vaccines provide significant benefits over DNA vaccines, in addition to the theoretical advantages of DNA vaccines over conventional classical immunizations.
Because the mRNA is translated in the cytoplasm rather than the nucleus, there is little possibility of the RNA becoming integrated into the host genome.
Modified nucleosides can be integrated into mRNA to reduce immune response activation and generate a longer-lasting impact through increased translation ability.
To boost antigen translation and hence immune response, an extra ORF coding for a replication mechanism might be inserted, reducing the quantity of starting material required.
Disadvantages of mRNA
Because mRNA is delicate, certain vaccinations must be stored at extremely low temperatures to prevent them from deteriorating and providing ineffective protection to the recipient.
While changes in LNP formulations or mRNA secondary structures may contribute to the thermostability variances, many experts believe vaccines will have similar storage needs and shelf life under various temperatures.
Several platforms are being investigated to see whether they can store at greater temperatures.
There is always a danger of unknown consequences because no mRNA technology platform (drug or vaccine) has been approved for use in humans before 2020.
The 2020 COVID-19 pandemic necessitated mRNA vaccines’ speedier production capabilities, making them appealing to national health organisations and sparking disagreement over the sort of first authorisation mRNA vaccines should receive following the eight-week post-final human testing phase.
Frequently asked questions
Q) What are the adverse effects to taking the mRNA vaccine?
Although, there are no such reactions to the vaccine but mRNA has been reported to trigger individuals who are prone to autoimmune reactions.
In order to minimise this effect, mRNA vaccination has taken steps to ensure sequences are intended to closely resemble those produced by host cells.
Q) Where did the vaccine’s mRNA originate?
All the mRNA vaccines are synthesised and produced in labs and the production of it has nothing to do with the involvement of any animal or human cells. Thus, it is completely safe and effective.
Q) Is it possible for the vaccine’s mRNA to remain in the DNA of human cells?
It cannot be incorporated into the DNA of the vaccinated cell since it is RNA. To put it another way, an mRNA vaccination cannot alter human DNA. Additionally, the RNA in the vaccination is rapidly broken down in the body.
Q) When should individuals who have tested positive for COVID 19 receive an mRNA vaccine?
Individuals who have recovered from an COVID should be urged to be vaccinated as soon as possible.
When compared to individuals who had not previously been infected with COVID-19 illness, side effects following immunisation have been observed to occur at equal or lower rates.
Q) Is it safe for individuals with heart problems to get the mRNA COVID 19 vaccine?
Cardiac problems are not considered contraindications to immunisation with COVID-19 mRNA vaccines in the vast majority of cases. COVID-19 mRNA vaccinations can be safely administered to people with the following cardiac disorders without the need for further monitoring or precautions:
coronary artery disease
heart illness caused by rheumatoid arthritis
congenital heart disease
cardiomyopathy after a heart transplant
heart abnormality (congenital)
For all those with a history of the following conditions, getting COVID-19 mRNA vaccinations is safe; however, they should talk to their doctor about the best time to get vaccinated:
- acute decompensated heart failure.
- current or recent myocarditis or pericarditis due to causes other than vaccination
- acute rheumatic fever or acute rheumatic heart disease
Q) What are the COVID 19 Vaccines’ side effects in children?
Discomfort at the injection site, weariness, headache, fever, chills, muscular pain, or joint pain were all reported in children aged 5 to 11 years old, and were comparable to those reported in other age groups. However, compared to other age groups, adverse effects were less common.
Although a rare number of occurrences of myocarditis, or heart inflammation, have been reported in teenagers and young adults, especially in the four days after the second dosage of the vaccine, this adverse effect has not been reported in children.