On April 29, the new coronavirus mRNA vaccine developed by Siwei (Shanghai) Biotechnology Co., Ltd. was approved by the State Food and Drug Administration and will carry out clinical trials. This vaccine contains D614G mutations in the R&D design of Delta, Olmi kerong and other virus variants, which has a protective effect on the current epidemic strains of the new crown virus. In addition, the phase II clinical trial carried out by Sigbi in Laos has been fully enrolled, and the existing trial data preliminarily shows that the product has good safety.
The mRNA vaccine has three main advantages
Since the outbreak of the new crown epidemic, the mainland government has deployed 5 technical routes, and the mRNA vaccine is one of them. At present, none of the vaccines developed by domestic companies have been approved for listing. The mRNA vaccine developed by Pfizer and Byntec and the mRNA vaccine developed by Modena have been authorized for emergency use by the drug regulatory authorities in many countries and regions.
the Chinese name of mRNA is messenger ribonucleic acid, which sends instructions to human cells and then creates a target protein or antigen that stimulates the body's immune response. The fat membrane wrapped in the new coronavirus particles has spike glycoprotein on the surface, which is the breakthrough of the mRNA vaccine targeting. Like messengers, mRNAs carry genetic information encoded by proteins and can be translated directly into proteins after being transmitted to ribosome machines. If it can be translated into S protein, it will cause the body to have an immune response to the new crown virus.
Li Hangwen, founder and chairman of Si Microbial, believes that this type of vaccine has three major advantages: one is high safety, there is no potential host infection risk or mutagenesis risk integrated into the host cell genome; second, the protection effect is good, which can not only induce humoral immunity of the human body, but also induce cell immunity; third, it is easy to produce, with the potential for rapid production, low cost and rapid expansion of production capacity.
Preliminary studies have shown that after receiving the mRNA vaccine booster needle, the human body has a strong defense against the Omikejong variant. In addition to defending against the coronavirus, mRNA technology can also encode other proteins for tumor treatment, rare disease treatment, gene editing, protein supplement therapy, infectious disease prevention, immunotherapy and other fields. At present, there are more than 150 mRNA vaccines and drug development pipelines in the world, most of which are in the early research or clinical trial stages.
What are the thresholds for mRNA technology
The development of mRNA vaccines and drugs is very difficult, and delivery technology is the core barrier. Shen Haifa, chief technology officer of Si Microbiology, introduced that the exposed mRNA molecules can not only not directly enter human cells, but also will be immediately degraded in the body, so efficient delivery technology is the greatest guarantee for the effect of such vaccines. The LPP (Lipid Polymer Complex) nano-delivery system developed by Shen Haifa and his team enables mRNA vaccines and drugs to have a three-dimensional nuclear shell structure, high immune recognition, strong safety, and its precise targeted function can also reduce toxic side effects.
"To accurately deliver mRNA transcribed in vitro to specific types of cells in order to complete targeted and inhaled drug delivery, we need continuous technical research in this regard." Li Hangwen said that many European and American enterprises have relatively complete delivery system patents, and they are investing a lot of manpower and material resources to develop new patented technologies, and domestic enterprises must catch up. At present, Smicrobi has mastered the core technology of mRNA vaccine and has the exclusive global interest in LPP nano-delivery system.
There are also many technical thresholds for the development of mRNA vaccines, such as the use of modified nucleosides and other technologies in the design and preparation of vaccines, which can significantly inhibit the body's immune recognition of exogenous mRNA, thereby reducing the toxic side effects of vaccines and improving the expression efficiency of mRNA. The purity of synthetic mRNA in vitro is also critical because double-stranded RNA impurities can be produced during mRNA synthesis, which is recognized by "pattern recognition receptors", resulting in unnecessary non-specific immune responses and inhibiting the production of candidate immunogens.
"In terms of modifying nucleosides to reduce side effects, Chinese companies are generally at the level of tracking the international frontier, lacking nucleoside modification methods and patent protection." Li Hangwen said that this will bring certain difficulties to the development of mRNA therapy in China, but more and more biomedical companies are investing in this new direction of research and development, which is expected to make breakthroughs.