How it works in nature and in vaccine production

vaccination Has been for a long time It is an integral part of public health programs around the world, reducing the spread and severity of infectious diseases.Success Immunization strategy Can be seen to protect children from diseases such as polio, hepatitis B, measles and to protect adults from influenza and pneumococcal infections Globally..

The COVID-19 pandemic has created an urgent need for effective vaccines.This is a messenger RNA (mRNA) vaccine Classification It attracted attention as a next-generation technology.Decades of research and clinical development into synthetic mRNA platforms for cancer treatment and vaccines for infectious diseases such as influenza, malaria and rabies have ultimately paid off as both. modern When Pfizer / BioNTech The COVID-19 mRNA vaccine has received an emergency use authorization. As a result, mRNA technology is gaining public attention.

Development of synthetic mRNA into a vaccine

Ribonucleic acid (RNA) is a natural molecule found in all our cells. There are many types of RNA, each with different functions. As the name implies mRNA functions as an important messenger in human cells.. These molecules have their own code that tells cells when to make which protein. The code is copied from a strand of DNA in the nucleus of the cell in a process called transcription. The mRNA is then transported to the cytoplasm (the solution contained in the cell), where the message is “read” and translated by the cell’s protein production mechanism. The result is important proteins such as enzymes, antibodies, hormones, and structural components of cells.

Scientists almost 40 years ago found That they can mimic transcription and produce synthetic mRNA without cells. This process, known as in vitro transcription, can generate many mRNA molecules from DNA strands in vitro. This requires enzymes (called RNA polymerases) and nucleotides (molecules that are components of DNA and RNA). When mixed together, the polymerase reads the strand of DNA and converts the code into a strand of mRNA by binding the different nucleotides in the correct order.

When in vitro transcribed mRNA is introduced into a cell, it is “read” by the cell’s protein production mechanism in a manner similar to that of natural mRNA. In principle, this process can be used to produce synthetic mRNAs that encode the protein of interest. In the case of vaccines, mRNA encodes a portion of a viral protein known as an antigen. When translated, the antigen provokes an immune response and provides protection against the virus. mRNA is short-lived and does not alter cellular DNA. Therefore, it is safe for the development of vaccines and treatments.

The main advantage of in vitro transcription is that it does not require cells to produce mRNA. It has manufacturing advantages over other vaccine technologies. For example, quick delivery and reduced risk of biological safety.only 25th We will produce a clinical batch of Moderna’s lipid nanoparticle mRNA vaccine candidate, which was the first COVID-19 vaccine to participate in human clinical trials in March 2020.

Importantly, because in vitro transcription is cell-free, the synthetic mRNA production pipeline is flexible and new vaccines and treatments can be streamlined to existing facilities. By replacing the DNA code, the facility can easily switch from producing one type of mRNA vaccine to producing another type of mRNA vaccine. This may prove to be essential not only to guarantee existing mRNA production facilities in the future, but also to provide rapid vaccine response to the outbreak of new pandemics and emerging infectious diseases.

How Does the mRNA Vaccine Work?

The mRNA vaccines we are familiar with today have benefited from years of research, design and optimization. Understanding how synthetic RNA is recognized intracellularly has proven essential to the development of effective vaccines. MRNA usually encodes a known viral antigen. For the COVID-19 mRNA vaccine, a sequence encoding the SARS-CoV-2 peplomer or receptor binding domain is used. The mRNA molecules that encode these antigens are incorporated into very small particles made primarily of lipids (fats). Lipid particles have two main functions. It protects mRNA from degradation and helps deliver it to cells. Once in the cytoplasm, mRNA is translated into an antigen that triggers an immune response.

This process is essentially an immune system training exercise, usually taking weeks for adaptive immunity to mature and synchronize. mRNA vaccine It is shown Stimulates both arms of the adaptive immune response, which is important for establishing protection. Humoral (B cell) immunity produces antibodies, and cell-mediated (T cell) immunity helps detect infected cells. The current schedule for the mRNA COVID-19 vaccine uses a two-dose (prime boost) approach aimed at enhancing the adaptive immune response against the SARS-CoV-2 virus.

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The COVID-19 vaccine produces T cell immunity that persists and acts against viral variants

Another type of mRNA vaccine. Self-amplified RNA, You may only need a single low dose to achieve the same level of protection. In the cell, these self-amplifying RNA vaccines can copy the mRNA code. This means that less RNA can produce more antigens.Several COVID-19 RNA vaccine Currently in clinical trials, we are exploring self-amplifying RNA technology.

RNA vaccine over COVID-19

This is an exciting time for mRNA technology. Large-scale production of mRNA drugs is becoming a reality, thanks to the cooperation of governments, funding agencies, academia, biotechnology and pharmaceutical companies.Success modern When Pfizer / BioNTech The COVID-19 vaccine helped reactivate ongoing mRNA research.

Both mRNA and self-amplifying RNA have shown potential as vaccines for multiple infectious diseases such as influenza, respiratory syncytial virus, rabies, Ebola hemorrhagic fever, malaria, and HIV-1.Especially coupled with therapeutic applications Immunotherapy For the treatment of cancer, mRNA technology continues to improve and expand, forming an integral part of future drug development.