The Development of mRNA Vaccine Technology: An Overview

  

The development of mRNA (Messenger Ribonucleic Acid) vaccine technology can be considered a medical breakthrough that has revolutionized science’s ability to develop measures to protect us from deadly diseases.

mRNA (messenger RNA) is a molecule in RNA that instructs cells to produce proteins. This technology uses mRNA to instruct cells to produce a specific protein that triggers an immune response that protects against a particular disease. One benefit of mRNA vaccine technology is that the technology can be quickly adapted to help fight against emerging infectious diseases.

For example, mRNA vaccine technology played a vital role in allowing science to develop vaccines to protect against COVID-19 rapidly. Two vaccines — from Moderna and Pfizer-BioN Tech — received emergency use authorization from the U.S. Food and Drug Administration (FDA) less than a year after the pandemic's start.

Versatility is another benefit provided by mRNA vaccine technology. Because the underlying mRNA technology does not change with every application, researchers can quickly create vaccines that target a range of diseases by altering the genetic code in the mRNA molecule. This flexibility is particularly important in rapidly evolving pathogens that may become resistant to traditional vaccine approaches.

This article will discuss mRNA technology, its early research and development, and the future scope of its use in the biopharmaceutical industry.

What is messenger ribonucleic acid (mRNA) technology?

mRNA technology is an effective and advanced technique in which synthetic mRNA can help create vaccines. mRNA is a genetic material that carries genetic information from DNA to the ribosomes serving template for protein synthesis.

mRNA vaccines usually contain a small piece of genetic material that encodes the viral protein. After an mRNA vaccine is injected into the body, cells are used as a template to produce a viral protein. The body’s immune system recognizes the viral protein and prepares an immune response against it. That creates immunity against the actual virus if the person is exposed to it in the future.

Unlike traditional vaccines, which can take years to develop and test, mRNA vaccines can be quickly designed and produced in response to new and emerging diseases. In addition, mRNA technology can be used to create vaccines tailored to specific pathogens. That makes it an excellent tool for tackling infectious diseases that could be difficult to treat with traditional vaccine methods.

For example, mRNA technology made it possible to create highly effective vaccines in response to the COVID-19 pandemic in record time. Another example is the development of mRNA vaccines for the Zika virus, a persistent threat a few years ago.

History of mRNA technology

The development of mRNA technology began in the early 1990s with the discovery of the ability of mRNA to produce proteins in a laboratory setting. Using mRNA as a therapeutic agent was first proposed in the early 2000s when researchers began to explore its potential as a tool for treating diseases, including cancer and genetic disorders. At the time, mRNA was considered a promising alternative to traditional protein-based therapeutics, which were tedious and expensive.

A key breakthrough in the development of mRNA technology came in 2005 when researchers at the University of Pennsylvania demonstrated that synthetic mRNA could help induce an immune response in mice. That discovery paved the way for mRNA vaccines, which have since been used to combat several infectious diseases, including COVID-19.

Researchers have continued to explore its potential uses since the mRNA's initial discovery as a therapeutic tool. Today, the development of mRNA technology is being investigated as a potential treatment for various diseases, including cancer, genetic disorders, and autoimmune diseases.

In addition to its potential therapeutic uses, mRNA technology is also being explored as a tool for basic research. Scientists are using mRNA to study the complex molecular processes that cater to various biological phenomena, from the development of embryos to the formation of memories in the brain.

The history of mRNA vaccine technology is summarized below.

 

 

Development of mRNA technology

A key advancement in mRNA technology was discovering how to deliver mRNA into cells without being degraded by the body's immune system. Additionally, lipid nanoparticles have been developed to encapsulate and protect mRNA to allow it to enter cells and produce proteins. This breakthrough has opened the doors for the use of mRNA in biopharmaceuticals.

Several companies are leading the way in developing mRNA technology, including Moderna, BioNTech, CureVac, and Translate Bio. Moderna was the first company to bring an mRNA vaccine to market with the approval of the Covid-19 vaccine. At the same time, BioNTech partnered with Pfizer to develop another Covid-19 vaccine utilizing mRNA technology that was approved for use shortly after.

The effectiveness of mRNA technology comes from its potential to change how we treat diseases. Because mRNA can instruct cells to produce proteins, researchers can create vaccines and treatments for various diseases, including cancer, genetic disorders, and infectious diseases.

mRNA vaccines have also been instrumental in the development of therapies. For example, scientists have developed an mRNA therapy for cystic fibrosis (a genetic disorder affecting the lungs and digestive system). Another promising area of research is using mRNA therapies for rare diseases, such as lysosomal storage disorders.

Covid-19 vaccines and mRNA technology

The Covid-19 pandemic brought mRNA technology to the forefront by making it possible to develop vaccines more quickly. The mRNA vaccines developed by Moderna and BioNTech/Pfizer were the first mRNA vaccines approved for use in humans.

These vaccines use mRNA to instruct cells to produce a protein found on the surface of the Covid-19 virus. That protein triggers an immune response that causes the body to recognize and fight the virus if it is encountered in the future. The mRNA vaccines have shown high efficacy rates and have been instrumental in the fight against the Covid-19 pandemic.

For example, the Pfizer-BioNTech vaccine was 95% effective at preventing COVID-19 in clinical trials involving thousands of participants. Similarly, the Moderna vaccine was found to be 94.1% effective at preventing COVID-19 in a similar set of clinical trials. These high efficacy rates have been a crucial factor in the success of vaccination campaigns to reduce the spread of COVID-19 and bring the pandemic under control.

The potential of mRNA technology

There is vast potential for mRNA technology in immunization and biopharmaceuticals. In addition to the Covid-19 vaccines, scientists could use mRNA to develop vaccines and treatments for many diseases, such as flu, Zika virus and rabies.

In the case of infectious diseases, mRNA vaccines have the potential for quick development and manufacturing in response to emerging outbreaks, just as they were for the COVID-19 pandemic.

mRNA vaccines do not contain any live virus. Instead, they contain only a small piece of genetic material instructing cells to produce a protein that triggers an immune response. That proved safe and effective in clinical trials, with no serious adverse effects reported.

In addition to vaccines, mRNA technology can open the doors to novel treatments for many diseases. For example, researchers are exploring using mRNA to deliver cancer treatments directly to tumor cells to help reduce the side effects of cancer treatment and improve patient outcomes.

Moderna’s Individualized neoantigen therapy (mRNA-4157) is an example of mRNA used for cancer treatments. Other vaccines, such as CureVac COVID-19 and Moderna COVID-19, influenza vaccines represent the mRNA’s utility in treating various diseases.

Additionally, the technology could treat genetic disorders by delivering healthy copies of genes to cells affected by a disease. One example is Moderna’s PCCA/PCCB Propionic acidemia (mRNA-3927). However, researchers must learn more about the applications of mRNA vaccine technology to help understand their efficacy in treating various autoimmune diseases.

Applications of mRNA vaccine technology

The development of mRNA vaccines may transform immunization because of its approach to fighting diseases. In addition to its potential to be effective in treating cancer and other illnesses, there are several other potential applications of mRNA vaccine technology, such as treating autoimmune diseases, gene therapy, and cancer immunotherapy.

Treatment for Autoimmune Disease

mRNA technology shows promise for treating autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, and lupus. When people have autoimmune diseases, their immune system mistakenly attacks healthy cells. With mRNA technology, scientists can create custom mRNA molecules that contain code for proteins and dampen the body’s immune response. That helps eliminate the harmful autoimmune response to treat many autoimmune diseases with minimal side effects.

Gene Therapy

mRNA technology can also be applied to gene therapy, which involves introducing new genetic material into a person's cells to treat or prevent disease. mRNA, often encoded by using CRISPR or MegaTALEN as a gene-editing tool, can deliver genetic material to cells without the unwanted side effects that can be caused by viral vectors or other delivery systems. That makes mRNA an attractive option for gene therapy because it is relatively safe and easy to use. Scientists have developed mRNA-based therapies for rare genetic diseases, such as cystic fibrosis and muscular dystrophy, with promising results.

Cancer Immunotherapy

Cancer immunotherapy is another potential application of mRNA technology. In this use, mRNA is used to encode cancer-specific antigens, which are then introduced into the body to stimulate an immune response against the cancer cells.

This approach has shown promise in early clinical trials, with some patients showing improved outcomes compared to traditional cancer treatments. mRNA immunotherapy has the potential to be an effective and relatively safe approach to treating a wide range of cancers, making it an exciting area of research.

Infectious Disease Vaccines

mRNA technology has already been used to develop vaccines against infectious diseases such as COVID-19. The flexibility of mRNA technology allows scientists to create vaccines for use against a wide range of pathogens, including viruses, bacteria, and parasites.

This approach could significantly change how we develop and deploy vaccines by providing a rapid and effective response to emerging infectious diseases. mRNA vaccines have shown great promise in clinical trials, with some demonstrating high levels of efficacy and excellent safety profiles.

To summarize, mRNA technology has many potential medical applications, from treating autoimmune diseases and genetic disorders to cancer immunotherapy and infectious disease vaccines. As research into mRNA technology continues, there will likely be additional breakthroughs and innovative uses in the coming years.

Challenges in innovating mRNA vaccine technology

While mRNA technology can be used effectively enough to treat various diseases, several challenges could impede its development and application. Some top challenges include:

Stability and Storage

mRNA is a fragile molecule that can easily break down, making it difficult to store and transport. That is particularly challenging for mRNA vaccines, which must be transported and stored at very low temperatures to remain effective. That is why Improvements in stability and storage technology will be critical for the widespread adoption of mRNA vaccines.

Manufacturing Scalability

mRNA vaccines are produced using a complex process that can be difficult to scale to meet global demand. With many process control and contamination concerns, many mRNA therapeutics manufacturers prefer the scale-out approach instead of the scale-up approach by adding additional manufacturing facilities instead of increasing product at an existing facility.

That means more space and resources would be needed to scale out mRNA manufacturing. As a result, manufacturers are working to develop new production methods and the infrastructure needed to produce mRNA vaccines at a large scale.

Encapsulation and formulation of mRNA therapy

Many manufacturers formulate and encapsulate mRNA in liquid nanoparticles (LNP) and liposomes to produce mRNA from the body’s immune system and to have tissue-specific delivery. Although there are specialized technology and instruments for mRNA encapsulation, the manufacturing process requires optimization of process parameters and the input materials, such as modification of phospholipids. These are all challenges companies must meet during the process development phase.

mRNA Downstream Purification

After in-vitro transcription, impurities such as DNA templates, NTPs, and aberrant mRNA must be separated from the desired mRNA. The lab purification process uses lithium chloride precipitation and is not easily scalable. As a result, chromatography has become the mainstream method in large-scale production.

Common chromatography methods include size exclusion (SEC), ion pair reverse phase (IPC), and ion exchange (IEC). Each method has its advantages and challenges. For example, IEC requires denaturing RNA, making the manufacturing process more complicated.

Affinity chromatography is a viable method in which resin binds to the poly-A tails of the single-stranded mRNA. stability and storage technology improvements lack of cost-effectiveness may not be attractive in all situations.

The future of mRNA vaccine technology

Despite existing shortcomings, the future of mRNA vaccine technology is promising. Several global organizations and companies are already leading the way in developing and producing mRNA vaccines, including:

• Moderna: This US-based biotechnology company was one of the first to develop an mRNA vaccine for COVID-19 and continues to be a leader in the field. Moderna is now developing mRNA vaccines for various diseases, including Zika and cytomegalovirus.
• Pfizer/BioNTech: This partnership between a US pharmaceutical company and a German biotechnology company produced one of the first mRNA vaccines authorized for use in the United States. Both companies have continued developing mRNA vaccines for other diseases, including influenza and cancer.
• CureVac: This German biotechnology company is developing an mRNA vaccine for COVID-19 and several other diseases, including rabies and influenza.

In addition to these companies, many other organizations and researchers are actively exploring the potential of mRNA technology. Some key focus areas for future innovation include:

• Developing more stable and durable mRNA molecules that can be stored and transported more easily.
• Improving manufacturing processes that can increase scalability and reduce the cost of producing mRNA vaccines.
• Expanding mRNA technology to treat diseases other than infectious diseases, including cancer and genetic disorders.
• Investigating the potential of mRNA technology as a tool for personalized medicine, in which therapies are tailored to the specific needs of individual patients.

To sum up, the future of mRNA vaccine technology is bright. With continued investment and innovation, mRNA technology has the potential to revolutionize the way we treat diseases and improve global health outcomes.

You can explore the future of medicine with Avantor Sciences’ mRNA technology and development. Contact us today to learn more about mRNA technology and its role in shaping medical care in the future.