Recently, scientists at Stanford University published a gene sequencing file of Moderna's COVID-19 vaccine on the open-source code repository GitHub, deciphering the mRNA sequence of the vaccine for the first time. The release immediately captured the headlines of major science and technology news websites, triggering an uproar in public opinion. For a while, it seems to have developed into a formula leakage incident that has attracted worldwide attention.

Facing public opinion, researchers claimed that the disclosure is helpful for the analysis of biomedical data, and will bring huge educational and economic value worldwide. Some scientists look positively because it is essential for people to distinguish the source of RNA (whether it is a vaccine or a virus) in medical practice. Although the RNA sequence information does make the vaccine more accessible in a sense, it is still difficult to establish a supply chain and actually produce the vaccine on a large scale.

It is reported that the work was completed by scientists from Stanford University, who said that the starting point is public welfare. With the popularity of the vaccine, its sequence information will appear in many examinations and diagnostic studies. Knowing these sequences and being able to distinguish them from other RNAs will be of great benefit to the analysis of future biomedical data sets. Specifically, they can help researchers or clinicians quickly determine that the sequence is a therapeutic mRNA rather than a host or source of infection during the sequencing process.

According to the researcher, the mRNA sequence information is only part of the vaccine that also contains more components in a complex construction method. For example, the synthesis and formulation steps included in the vaccine production process, such as preparation and encapsulation, involve very complex synthetic chemistry, enzyme chemistry, and membrane dynamics. Scientists from both Modena/NIH and BioNTech/Pfizer have done excellent work in these areas. Obviously, the publication of vaccine mRNA sequences does not mean that others can easily imitate vaccines. Former FDA commissioner and Pfizer board member Scott Gottlieb believes that the real bottleneck of vaccination is mainly supply and production instead of intellectual property restrictions.

The raging COVID-19 has made the development of mRNA vaccines feverish. The speed of vaccine development has also exceeded expectations, which not only proves that the biotechnology and pharmaceutical industries can respond to urgent and unmet global needs, but also proves the inherent ability of mRNA as a medicine. Compared with conventional vaccines, mRNA vaccines have the advantages of low cost, high production efficiency, and high safety, and have the potential to synthesize any kind of protein, which, therefore, have great application potentials against new infectious viruses that traditional vaccines cannot deal with. However, due to the instability of mRNA molecules, high innate immunogenicity, and low delivery efficiency in vivo, the application of mRNA vaccines has been limited. To realize the wide application of mRNA vaccines, it is necessary to focus on the delivery technology. The development of an efficient and non-toxic delivery system ( is the key to the success of the mRNA vaccine.

The determinants of the performance of mRNA delivery systems are multiple and interactive.
* The ability to deliver to appropriate cells and effectively release mRNA to the cytoplasm of the translation mechanism.
* The adjuvant properties, which can enhance immune response.
* Minimize the possibilities of adverse events or toxicity that may be caused by excessive inflammation at the injection site or systemic distribution and targeted expression.

Application of lipid nanoparticles in current clinical trials of SARS-CoV-2 vaccines

1. BioNTech/Pfizer
Acuitas ALC-0315 combined with DSPC, cholesterol, and polyethylene glycol-lipid is the delivery system in BioNTech's test.

2. Moderna
In Moderna’s research, the immunogen encoded by the nucleoside modified mRNA is a transmembrane anchored dialanine stable fusion pre-peak, with a natural furin cleavage site, and transmitted in LNP, which follows prototype MC3 LNP, but uses lipid H (SM-102) instead of MC3.

3. CureVac
CureVac's mRNA vaccine CVnCoV is a sequence-optimized mRNA-based vaccine encapsulated by lipid nanoparticles (LNP), which encodes a full-length, pre-fused, and stable S protein.

4. Translate Bio
Translate Bio uses unmodified mRNA to encode a double mutant form of double proline stabilized spike protein to deliver ionizable lipid C12-200 in the form of LNP, but it may be from ICE or a family of ionizable lipids based on cysteine.

5. Arcturus
Arcturus Therapeutics' LUNAR-COV19 is an extremely low-dose, potential single-shot self-replicating mRNA vaccine without any viral substances or adjuvants.

6. Imperial College London
The self-amplified RNA vaccine delivered in Acuitas LNP developed by Imperial College London can effectively inject new genetic code into human muscles, guiding the muscles to produce a protein that appears on the surface of SARS, thereby inducing protective immune responses.

Author's Bio: