Investment logic
The "14th five year plan" for the pharmaceutical industry has been issued and relevant pipelines under research have been continuously promoted. We are optimistic about the large demand for mRNA vaccine and related products in its upstream supply chain. The "fourteenth five year plan" for the development of pharmaceutical industry clearly points out: closely follow the development trend of vaccine technology, support the construction of mRNA vaccine, and improve the guarantee level of vaccine supply chain. Support vaccine enterprises to cooperate with important raw and auxiliary materials, consumables, production equipment and packaging materials enterprises to improve the quality and technical level of various products. In addition, with the continuous progress of domestic mRNA vaccine research and development in the near future and the progress of clinical and marketing of related products, the demand for upstream supply chain is increasing. Therefore, we are optimistic about the investment opportunities of mRNA vaccine and its upstream supply chain.
The production process of mRNA vaccine can be roughly divided into the following three stages:
Preparation of DNA stock solution: plasmid DNA amplification is usually amplified by E. coli fermentation. Starting from the recovery of strains, the production of plasmid DNA mainly goes through the steps of fermentation and culture, harvest and clarification, refining and purification, linearization, sub packaging and storage.
Preparation of mRNA stock solution: in this stage, mRNA is mainly prepared by using the linear DNA in the previous stage of in vitro transcription (IVT) as the temsector. The main process steps include transcription of linearized plasmid DNA into mRNA, chemical modification (including 5 'end capping structure (CAP) and 3' - Polya tailing structure), separation and purification, and sub packaging and freezing of mRNA stock solution.
MRNA preparation: the key preparation technology breakthrough has solved the problem of mRNA's medicinal properties. The main process links of mRNA preparation include mRNA encapsulation / loading, complex purification, sterilization and filtration, aseptic filling, etc.: among them, the basis of encapsulation / loading process is the design and development of delivery system.
The key links in the upstream supply chain / industrial chain of mRNA vaccine production include enzyme, plasmid, lipid raw materials, purification and quality control.
The production, extraction and purification processes of plasmids are relatively mature, and they can build their own production lines or outsource them.
The modified structure of mRNA plays an important role in stability, translation efficiency and immunogenicity, involving a variety of raw enzymes: in addition to plasmid DNA temsector, in vitro transcription also requires nucleoside triphosphate (NTPs) substrate, 5 '- cap analog, RNA polymerase, capping enzyme, poly (a) polymerase, inorganic pyrophosphatase and RNase inhibitor. Well designed mRNA modification structure is helpful to improve its stability and translation efficiency, prolong its half-life, reduce immunogenicity and so on.
The delivery technology platform is one of the key technologies of mRNA drugs. Lipid nanoparticles (LNPS) are the mainstream mRNA delivery system.
Quality control is also the key to the formation of safe and effective vaccine preparations. In this process, lnp-mrna is mainly detected by capillary electrophoresis, liquid chromatography, mass spectrometry and other instruments. At present, the localization rate in this field is low and domestic substitution is difficult.
Investment advice
It is suggested to pay attention to Nanjing Vazyme Biotech Co.Ltd(688105) , kingship biotechnology, Jenkem Technology Co.Ltd(688356) , Suzhou Nanomicro Technology Co.Ltd(688690) , Focused Photonics (Hangzhou) Inc(300203) , etc.
Risk tips
R & D progress is less than expected or fails, mRNA vaccine adverse reactions or safety risks, market approval progress is less than expected, market competition intensifies, raw material supply chain shortage and other risks.
