Since the COVID-19 epidemic, Pfizer and Moderna have used mRNA technology in a vaccine to help humans fight COVID-19. While mRNA technology is new to the public, the research has been around since the early 1990s.

What is an mRNA vaccine?

An mRNA vaccine is a vaccine that uses a molecular copy of messenger RNA (mRNA) to generate an immune response. Such vaccines deliver mRNA molecules into the body's immune cells, where they deliver a specific set of instructions to make protein fragments used by certain viruses. These protein molecules stimulate an adaptive immune response, teaching the body to recognize and destroy the corresponding viral attack. Using this technology, scientists have been experimenting with the potential use of mRNA for deadly diseases such as influenza, Ebola and SARS. Scientists have been experimenting with the use of mRNA therapy to develop personalized cancer treatments, as well as to develop vaccines against infectious diseases such as Zika virus. Scientists are also exploring whether mRNA therapy could be used as a protein replacement therapy for rare diseases such as the blood clotting disorder hemophilia.

mRNA vaccines have developed rapidly in the past two years of the epidemic, and the entire industry chain has now formed a behemoth, including incoming capital, production capacity in the hundreds of millions, and countless related workers.

But it is clear that there is only one product that supports this huge industrial chain - the new crown mRNA vaccine. But as per capita vaccination rates have increased, the market for mRNA vaccines for COVID-19 has declined in various expectations.

If mRNA doesn't find the next support point as soon as possible, it is actually difficult to maintain the "mRNA myth" by relying on the COVID-19 mRNA vaccine alone, so you can see that both Moderna and BioNTech are hurrying to carry out multi-party cooperation or develop new products by themselves.

When we talk about mRNA technology, we have to start with the central principle that DNA transports mRNA, and mRNA is translated into proteins, so as to achieve the cytoplasmic transmission of the genetic material of life.

In mRNA technology, mRNA that can encode a specific protein is delivered directly into human cells so that the cells translate the mRNA to express the target protein, either to activate the immune system's response to the protein (which is the mechanism of mRNA vaccines), or to replenish disease-causing proteins that the body lacks, and so on.

Since mRNA technology can enable cells to produce any information, it has a broad application prospect, including antiviral, tumor, protein deficiency/error diseases, and other types of diseases.

Virus vaccines & Tumor vaccines

In fact, mRNA technology is currently best known for its use in vaccines.

Based on the success of the COVID-19 mRNA vaccine, mRNA projects targeting various viral infections have also been launched, mostly based on the same basic principles.

Design mRNA that encodes viral fragments, and then inject them into the human body, so that cells produce viral proteins, thereby activating the human immune system to fight the virus and establish memory immunity to the disease. Once in the environment, the body is exposed to the virus, the body's immune system is activated again to fight the virus.

mRNA is in the direction of vaccines, in addition to antiviral vaccines, there is also a type of vaccine - tumor vaccines. However, compared with antiviral vaccines, the development of tumor vaccines is still relatively early (the leading echelon is generally in clinical phase 1), and there are more challenges to be solved.

First of all, the target problem of tumor vaccines is more eye-catching. Compared with the single target of virus vaccines, mRNA tumor vaccines usually encode twenty or thirty target proteins. This is also due to the variable target of mutation in tumor cells, while avoiding tumor target loss.

Secondly, mRNA tumor vaccines, as far as we currently understands, are mostly autologous products. This will also lead to a cost and price issue, which we will not discuss much, but can refer to CAR-T cell therapy.

In general, it is better to be optimistic about the next mRNA virus vaccine than to expect the overtaking of mRNA tumor vaccines.

mRNA therapy

The therapeutic use of messenger RNA (mRNA) has fueled great hope to combat a wide range of incurable diseases. Under the assumption of mRNA therapy, many diseases can be treated.

Therapeutic applications include:
(1) Protein replacement to restore the function of a single protein for rare single-gene diseases;
(2) Cell reprogramming, mRNA can regulate cell behavior by expressing transcription or growth factors;
(3) Immunotherapy, in which mRNA-encoded transcripts elicit specific immune responses against target cells, such as therapeutic antibodies, to express virtually any desired protein in host cells and tissues and preserve host cell-intrinsic encoding Post-translational modification of proteins.

For mRNA therapy, low immunogenicity, high stability, and efficient translation are required by design. However, the expression of mRNA vaccines is transient and will degrade over time. Therefore, for chronic diseases, mRNA therapy is a long-term medication regimen.

Secondly, the delivery of mRNA is still dominated by lipid nanoparticles (LNPs). Lipid Nanoparticle (LNP) is currently the dominant delivery system. They are often used in vaccines due to their relatively easy uptake by antigen-presenting cells. The three major mRNA vaccine giants Moderna, CureVac and BioNTech are currently using LNP delivery technology for their COVID-19 vaccines. According to the current research reports, LNP technology is still insufficient and may have potential toxic and side effects. In addition, the current targeting of mRNA-LNPs is dominated by the liver, lung, and heart, and for other organs and cell types, new delivery technologies need to be developed.

In the field of mRNA therapy, CureVac Chief Financial Officer Pierre Kemula said in an interview that the eye may be a good breakthrough, with an independent treatment window and a safer dose.

mRNA gene editing

mRNA gene editing is also an emerging application of mRNA technology. Using mRNA to express Cas9 or other proteins in CRISPR gene editing technology can avoid the risks associated with the integration of nucleases into the host genome.

In this application area, the transient expression of mRNA becomes a unique advantage. The transient nature of mRNA expression limits intracellular nucleases, reducing the risk of off-target cleavage and immune responses to the Cas9 protein.

Conclusion

As a new pharmaceutical technology, mRNA has made breakthroughs in the treatment of infectious diseases and tumors in a short time. As a new technology, mRNA technology still has many areas to be developed, including various application areas and disease treatment. As science continues to advance, mRNA technology is expected to improve more disease treatments in the future.

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