June 30, 2022

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Opportunities and challenges of mRNA technology:  Where is its potential frontier?

Opportunities and challenges of mRNA technology:  Where is its potential frontier?



 

Opportunities and challenges of mRNA technology:  Where is its potential frontier?



mRNA technology has developed rapidly due to the COVID-19 vaccine. Many experts have begun to think about the development prospects of mRNA after the COVID-19 epidemic?

 

Recently, researchers from the Alliance for Epidemic Preparedness Innovations (CEPI) , a global health non-profit organization , analyzed the development prospects of mRNA from the following aspects. The related article The mRNA vaccine development landscape for infectious diseases was published in Nature .

 



From the characteristics of mRNA vaccines, we can see the future prospects


Opportunities and challenges of mRNA technology:  Where is its potential frontier?

 

First of all, from the perspective of developers, there are about 90 mRNA vaccine-certified R&D institutions in the world.

These institutions have a total of 137 vaccines under development, of which 76% are still in the experimental stage, and 24% have entered the clinical stage.

 

Opportunities and challenges of mRNA technology:  Where is its potential frontier?a. Leaders in different countries and regions b. Carrier tools for wrapping RNA
c. The main diseases targeted by mRNA in the clinic d. The distribution of mRNA manufacturers

 



But the situation in vaccine development is changing rapidly. Due to factors such as intellectual property rights, drug costs, lack of materials, and limited professional and technical personnel, low- and middle-income countries cannot implement mRNA vaccines. 

Most mRNAs are led by biopharmaceutical companies in Asia, Oceania and North America.


Opportunities and challenges of mRNA technology:  Where is its potential frontier?mRNA vaccine trials currently being clinically advanced around the world

 



The COVID-19 virus is a pandemic virus, and no country in the world is immune.

Therefore, pharmaceutical companies in many countries negotiate with vaccine manufacturers in low- and middle-income countries for mutual benefit and win-win results.

One side provides technology, and the other side provides market and resources. Thanks to this, low- and middle-income countries have been able to obtain many mRNA vaccines.



Secondly, in the field of mRNA technology, the first is the structure of mRNA.

Researchers need to ensure that mRNA can accurately encode a certain part of the virus and induce an immune response in the human body.

The second is the carrier tool for encapsulating nucleic acid.

More than half of them are currently The developed vaccines are delivered using lipid nanoparticles (LNPs) .



As we all know, RNA is a long-chain molecule condensed by ribonucleotides through phosphodiester bonds, and a ribonucleotide molecule is composed of phosphoric acid, ribose sugar and base.

Because it contains a lot of phosphoric acid, the nucleic acid is negatively charged.



As a result, scientists found a positively charged lipid on the surface, which often has an amine group on the surface, which can be positively charged in an acidic environment.

Therefore, cationic liposomes can be well combined with phosphate through electrostatic interaction to form a relatively stable lipid complex.



For preventive vaccines, stability and tolerance are its core development factors. At present, more than 1 billion doses of the COVID-19 vaccine have been vaccinated, so a large number of mRNA vaccines using LNP may appear in future preventive medicine.



Furthermore, in terms of the pathogen targets targeted by mRNA, more than 80% of the existing mRNA vaccines are directed against the COVID-19 vaccine, and in the future, people will also expand towards pathogens such as influenza, bacteria, and parasites.



Finally, there is the issue of globalization of vaccine manufacturers.

WHO has been pinning its hopes on promoting mRNA technology on a global scale.

However, given that mRNA technology requires many specialized technologies and raw materials, such as plasmids, DNA templates, DNA enzymes, etc., these technologies and resources are very scarce, thus hindering the progress of the globalization of this technology.

 

 



mRNA technology also faces many challenges


Opportunities and challenges of mRNA technology:  Where is its potential frontier?Key challenges for mRNA vaccines

 

 

The development of mRNA also faces many challenges.

For example, in the research and development of vaccines, researchers hope to provide more valent vaccines. In short, the same vaccine is used to control more similar viruses.

For example, the HxNx virus is a rapidly changing virus, and the new coronavirus A variety of variants have also been derived, so improving the “composite type” of the vaccine is beneficial to the COVID-19 vaccine’s resistance to changes in the virus.



Clinically, researchers have also encountered a lot of troubles, such as the expression of type I IFN (IFN-α and IFN-β) easily induced by multiple receptors of mRNA itself, accompanied by the production of pro-inflammatory cytokines.

The immunogenicity of mRNA inhibits the translation and expression of mRNA, and it is easy to make mRNA ineffective.



In addition, it is also necessary to consider whether the vaccine can stimulate the human immune response to produce immune protection and the protection time of the vaccine.

A short-term failure could make people who were vaccinated some time ago re-infected, etc., which could lead to an out-of-control epidemic situation.



Another real problem is that many poor countries do not have constant temperature storage technology and well-trained nurses to store mRNA vaccines or inject them into the human body well, and some low- and middle-income countries cannot conduct clinical trials due to the control of clinical trial equipment. .

 



Outlook


However, challenges also portend opportunities.

The COVID-19 epidemic has accelerated the development of mRNA vaccine technology, and the successful implementation of Pfizer and other vaccines has demonstrated the excellent control and unlimited potential of mRNA in pandemic infectious diseases.



Many mRNA developers are actively investing in multiple expandable channels and upgrading mRNA technology, which is also the breakthrough goal of mRNA in the future.

In order to ensure more effective control of the pandemic, researchers still need to improve the stability of mRNA technology and expand the depth and breadth of research.



At present, the global health nonprofit Coalition for Epidemic Preparedness Innovations (CEPI) has drawn up an ambitious $3.5 billion plan to deal with possible future pandemics, hoping to create a better and stronger vaccine platform.

Most recently, the consortium is advancing RNA vaccines and vaccine banks to control endemic outbreaks of infectious diseases.

 

We may have just begun to tap the potential of mRNA technology.

 

 



References
[1] Arun Kumar. et al.(February 11, 2022). The mRNA vaccine development landscape for infectious diseases. Nature. https://www.nature.com/articles/d41573-022-00035-z

Opportunities and challenges of mRNA technology:  Where is its potential frontier?

(source:internet, reference only)


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